NZ537870A

NZ537870A - New effector conjugates, process for their production and their pharmaceutical use

Info

Publication number: NZ537870A
Application number: NZ537870A
Authority: NZ
Inventors: Markus Berger; Gerhard Siemeister; Ulrich Klar; Jorg Willuda; Andreas Menrad; Klaus Bosslet
Original assignee: Schering Ag
Priority date: 2002-07-31
Filing date: 2003-07-31
Publication date: 2007-03-30
Also published as: BR0313043A; IL166039A0; CO5700741A2; PL374528A1; WO2004012735A2; AU2003253365A1; NO20051038L; IS7708A; HRP20050186A2; MXPA05001282A; KR20050026033A; WO2004012735A3; CA2492437A1; ECSP055626A; EP1524979A2; JP2006505627A

Abstract

Conjugates of epothilones and epothilone derivatives (as effectors) with suitable biomolecules (as recognition units) are disclosed. Their production is carried out by the effectors being reacted with suitable linkers, and the compounds that are produced are conjugated to the recognition units. The pharmaceutical use of the conjugates for treating proliferative or angiogenesis-associated processes is described.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number 537870 537870 WO 2004/012735 PCT/EP2003/008483 1 New Effector Conjugates, Process for their Production and their Pharmaceutical Use The development of the understanding relating to the recognition of binding regions, especially in the field of monoclonal antibodies or fragments thereof against specific tumor antigens, makes it possible to consider a selective tumor therapy by specific release of an anti-tumor active agent at the target site. A precondition for such an approach, in which a highly active (toxic) active agent (effector) is coupled to a high-molecular, tumor-specific recognition unit, such as, for example, to an antibody, is a substantial inactivity of the conjugate, whose minimum components are represented by a recognition unit and an effector, until it has reached the target site (tumor). Arriving at the target site, the conjugate binds to the cell surface and the active ingredient, optionally after the preceding internalization of the entire complex, can be released. The successful therapy of solid tumors, especially with monoclonal antibodies, can be limited, however, by an inadequate penetration of the antibody into the tumor as well as the heterogeneous dispersion of the corresponding tumor-associated antigens in the tumor tissue. These limitations could be avoided in that the tumor-vascular system is attacked in a specific way. The growth of tumors below a volume of about 2 mm depends on a neoangiogenesis. The subsequent tumor growth is based on an intact vascular system, which ensures the supply with nutrients or the removal of waste products. The selective destruction of this system should therefore result in a necrosis of the tumor. The attack on the vascular system of the tumor promises a number of advantages relative to the direct attack on the tumor itself. In comparison to tumor cells, endothelial cells are easier to access, since no tumor tissue has to be penetrated. The damage of an individual tumor vessel should result in a necrosis of thousands of tumor cells. To damage a tumor vessel, it is not necessary to kill all endothelial cells. The specific attack of endothelial cells in or close to the tumors minimizes systemic side effects. Endothelial cells are genetically very stable, so that the probability of a development of resistance against the tumor therapeutic agent is low. 13/12 2004 MON 17:57 FAX +49 89 21029633 df-np Munich Schering 10009/011 10 Within the scope of this invention, surprisingly enough, a possibility has now been found to link the chemically very sensitive, highly-functionalized class of active agents of epothilones and analogs thereof to a high-molecular recognition unit via different linkers in different positions of the active agent. The object of this invention is thus, inter alia, 1. to find a method to link highly active active agents from the structural class of the epothilones and epothilone derivatives to suitable linkers, 2. to synthesize suitable linkers, 3. to develop a method to link these epothilone-linker conjugates to recognition units, such as, for example, monoclonal antibodies or fragments thereof, to form immune conjugates that are both chemically and metabolically sufficiently stable for the development of a pharmaceutical, and that are superior to the 15 epothilones or epothilone derivatives that are taken as a basis with respect to their therapeutic range, their selectivity of action and/or undesirable toxic side effects and/or the degree of their activity. This invention accordingly comprises effector conjugates of general formula I R\ R5 C—W I, in which 20 R.1a, R^, independently of one another, are hydrogen, Cj-Cjo alkyl, aryl, aralkyl, or together a -{0112)01 group, in which m is 2 to 5, R2a} R2b> independently of one another, are hydrogen, Cj-Cio alkyl, aryl, aralkyl, or together a-{CH2)n group, in which n is 2 to 5, or C2-C10 AMENDED SHEET 13/12 2004 MON 17:57 FAX +49 89 21029633 df-fflp Munich ->■» Schering 1010/011 alkenyl, or C2-C10 alkynyl, R3 is hydrogen, Cj-Cjo alkyl, aryl or aralkyl, and R^a, R^b, independently of one another, are hydrogen, Ci-Cjo alkyl, aryl, aralkyl, or together a -(CH2)p group, in which p is 2 to 5, 5 R5 is hydrogen, Cj-Cjo alkyl, aryl, aralkyl, CO2H, C02alkyl, CH2OH, CH20Alkyl, CH20Acyl, CN, CH2NH2, CH2N(alkyl, acyl)lj2, or CH2Hal, Hal is a halogen atom, R^, R7 jn each caslfare hydrogen, or together an additional bond, or together an 10 oxygen atom, or together an NH group, or together an N-alkyl group, or together a CH2 group, and G is an oxygen atom or CH2, D-E is a group H2C-CH2, HC=CH, C=C, CH(OH)-CH(OH), CH(OH)-CH2, O 4 \ CH2-CH(OH), HC_CH, 0-CH2, or, if G represents a CH2 group, 15 D-E is also CH2-O, W is a group C(=X)R8, or a bi- or tricyclic aromatic or heteroaromatic radical, 1,3 is hydrogen, or, if a radical in W contains a hydroxyl group, forms a group O-L4 with the latter, or, if a radical in W contains an amino group, 20 forms a group NR^^-L^ with the latter, R25 is hydrogen or C j -C] q alkyl, Sl AMENDED SHEET WO 2004/012735 PCT/EP2003/008483 4 X is an oxygen atom, or two OR^O groups, or a C2-C10 alkylenedioxy that may be straight-chain or branched, or H/OR^, or a CR^R* 1 group, R8 is hydrogen, Cj-Cio alkyl, aryl, aralkyl, halogen or CN, and R9 is hydrogen or a protective group PG^ r10, r1 1 in each case independently of one another, are hydrogen, C1-C20 aryl, aralkyl, or together with a methylene carbon atom form a 5- to 7-membered carbocyclic ring, Z can represent oxygen or H/OR* 2, A-Y can represent a group 0-C(=0), O-CH2, CH2-C(=0), NR^ 1 -C(=0) or NR21-S02, r20 can represent C1-C20 alkyl, r21 can represent a hydrogen atom or C^-Cio alkyl, PGX, PgY and PG^ can represent a protective group PG, and Ll, L2, and L^, independently of one another, can represent hydrogen, a group C(=0)C1, a group C(=S)C1, a group PG^ or a linker of general formula (HI) or (IV); provided that at least one substituent L1, L2 or L4 represents a linker of general formula (III) or (IV); the linker of general formula (III) has the following structure, T group alkyl, Rl2 can represent hydrogen or a protective group PG^, HI, WO 2004/012735 PCT/EP2003/008483 5 in which T can represent oxygen or sulfur, U can represent oxygen, CHR22, CHR22-NR23 -C(=0)-, CHR22-NR23-C(=S)-, 0-C(=0)-CHR22-NR23_C(=0)-, 0-C(=0)-CHR22-NR23-5 C(=S)-orNR24a, o can represent 0 to 15, V can represent a bond, aryl, a group •NR24b-C(=0)-0-(CH2)s—O u or a group NR24b-C(=S)-0-(CH2)s—O u s can represent 0 to 4, Q can represent a bond, 0-C(=0)-NR24c, 0-C(=S)-NR24c? -0-C(=0)-NR24C—-0-C(=S)-NR24c— ,or R22 can represent hydrogen, Cj-Ciq alkyl, aryl or aralkyl, 15 R23 can represent hydrogen or Cj-Cjo alkyl, R24a^ R24b5 and r24c} independently of one another, can represent hydrogen 10 or Ci-Cio alkyl, q can represent 0 to 15, WO 2004/012735 6 PCT/EP2003/008483 O * 11 o Af Af FG* can represent Cj-Cio alkyl-S3, ° , , Br , Cl . ° , or CO2H; and the linker of general formula (IV) has the following structure, T) (CHjt-W^-CX-OJ-U—(CH2)—FG1 in which T can represent oxygen or sulfur, W1, W2 are the same or different and can represent oxygen or NR24a, 0 can represent 0 to 5, 10 R22 can represent hydrogen, C1-C10 alkyl, aryl or aralkyl, R23 can represent hydrogen, or C1-C10 alkyl, R24a can represent hydrogen or C1-C10 alkyl, R27 can represent halogen, CN, NO2, CO2R28, or OR28, R28 can represent hydrogen, C1-C10 alkyl, aryl or aralkyl, 15 q can represent 0 to 5, U can represent oxygen, CHR22, CHR22-NR23-C(=0)-, CHR22-NR23- C(=S)- or C1-C20 alkyl, r can represent 0 to 20, 20 FG1 can represent C1-C10 alkyl-S3, WO 2004/012735 PCT/EP2003/008483 Xf Xf Br CI 0 , or CO2H, as a single isomer or a mixture of different isomers and/or as a pharmaceutically acceptable salt thereof. In addition, the invention describes the production of effector recognition unit conjugates of general formula (I), wherein the substituents therein have the above-mentioned meanings, but at least one group FG1 is replaced by a group FG2a or FG2b, wherein FG2a or FG2b can have the following meanings: FG2a: -S-S-, FG2b: -CONH- and wherein a recognition unit is conjugated via a sulfur atom with the group FG2a, wherein the indicated sulfur atom is a component of the recognition unit, or via an amide function of group FG2b, wherein the indicated nitrogen atom is a component of the recognition unit; wherein the recognition unit can be, for example, a peptide, a soluble receptor, a cytokine, a lymphokine, an aptamer, a spiegelmer, a recombinant protein, a framework structure, a monoclonal antibody or a fragment of a monoclonal antibody. According to this invention, the above-mentioned effector recognition unit conjugates can comprise one or more recognition units; in this case, the recognition units that belong to a conjugate can be identical or different. It is preferred that the recognition units of a conjugate be identical. The effector recognition unit conjugates according to the invention can be used in the form of their a-, (3- or y-cyclodextrin-clathrates or in the form of liposomal or pegylated compositions. The conjugates according to the invention are preferably used for the treatment of diseases that are associated with proliferative processes. For example, the therapy of different tumors, the therapy of inflammatory and/or neurodegenerative diseases, such as multiple sclerosis or Alzheimer's disease, the therapy of angiogenesis- Intellectual Property Office of N.Z. WO 2004/012735 8 iWl 8483 RECEIVED associated diseases such as the growth of solid tumors, rheumatoid arthritis or diseases of the ocular fundus, can be mentioned. The production of epothilones, their precursors and derivatives of general formula I is carried out according to the methods that are known to one skilled in the 5 art, as they are described in, for example, WO 00/50423, WO 98/25929, WO 99/58534, WO 99/2514, WO 99/67252, WO 99/67253, WO 99/7692, EP 99/4915, WO 00/485, WO 00/1333, WO 00/66589, WO 00/49019, WO 00/49020, WO 00/49021, WO 00/71521, WO 00/37473, WO 00/57874, WO 01/92255, WO 01/81342, WO 01/73103, WO 01/64650, WO 01/70716, US 6204388, US 6387927, US 6380394, US 10 02/52028, US 02/58286, US 02/62030, WO 02/32844, WO 02/30356, WO 02/32844, WO 02/14323, and WO 02/8440. As alkyl groups Rla, Rlb, R2* R2b r3 R4a R4b R5 r8? r10} rII, r20, R2l, R22, R23, R24a? R24b} r24c# r25 and R2^, straight-chain or branched-chain alkyl groups with 1-20 carbon atoms can be considered, such as, for example, methyl, 15 ethyl, propyl, isopropyl, butyl, isobutyl, tert.-butyl, pentyl, isopentyl, neopentyl, heptyl, hexyl, and decyl. Alkyl groups Rla, Rlb, R2a, R2b, r3, R4a R4b r5s r85 r10} rII, r20, r21} r22, r23} R24a? R24b} r24c r25 and r26 can also be perfluorinated or substituted by 1-5 halogen atoms, hydroxy groups, Cj-C^alkoxy groups or Cg-C^-aryl groups 20 (which can be substituted by 1-3 halogen atoms). As aryl radicals Rla, Rlb, R2a, R2b, R3, R4a R4b r5} r8} r10} r1 1? r22} R2^ and V, substituted and unsubstituted carbocyclic or heterocyclic radicals with one or more heteroatoms, such as phenyl, naphthyl, furyl, thienyl, pyridyl, pyrazolyl, pyrimidinyl, oxazolyl, pyridazinyl, pyrazinyl, quinolyl, thiazolyl, benzothiazolyl or 25 benzoxazolyl, which can be substituted in one or more places by halogen, OH, O-alkyl, C02H, C02-alkyl, -NH2, -N02, -N3, -CN, C^C^-alkyl, C^Q-acy! or C^q- acyloxy groups, are suitable. The heteroatoms can be oxidized provided that this does not cause the aromatic character to be lost, such as, for example, the oxidation of a pyridyl to a pyridyl-N-oxide. carbocyclic or heterocyclic radicals with one or more heteroatoms such as naphthyl, anthryl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolyl, isoquinolyl, benzoxazinyl, benzofuranyl, indolyl, indazolyl, quinoxalinyl, tetrahydroisoquinolinyl, 30 As bicyclic and tricyclic aryl radicals W, substituted and unsubstituted, WO 2004/012735 9 PCT/EP2003/008483 tetrahydroquinolinyl, thienopyridinyl, pyridopyridinyl, benzopyrazolyl, benzotriazolyl, or dihydroindolyl, which can be substituted in one or more places by halogen, OH, O-alkyl, C02H, C02-alkyl, -NH2, -N02, -N3, -CN, Ci-C20-alkyl, Ci-C20-acyl or C^ C2o-acyloxy groups, are suitable. The heteroatoms can be oxidized provided that this does not cause the aromatic character to be lost, such as, for example, the oxidation of a quinolyl to a quinolyl-N-oxide. The aralkyl groups in R^a, R^, R^a, R2b; r3; R4a? R4b r5s r8; rIO^ r113 r22 ^ r26 can contain in the ring up to 14 C atoms, preferably 6 to 10 C atoms, and in the alkyl chain 1 to 8 atoms, preferably 1 to 4 atoms. As an aralkyl radical, for example, benzyl, phenylethyl, naphthylmethyl, naphthylethyl, fiirylmethyl, thienylethyl or pyridylpropyl is suitable. The rings can be substituted in one or more places by halogen, OH, O-alkyl, C02H, C02-alkyl, -N02, -N3, -CN, Ci-C2o-alkyl, Ci-C20-acyl or Ci-C2Q-acyloxy groups. As representatives of protective groups PG, tris(Cj-C2o alkyl)silyl, bis(Ci-C2o alkyl)-arylsilyl, (C^-C2o alkyl)-diarylsilyl, tris(aralkyl)-silyl, C]-C2o-alkyl, C2-C2q-alkenyl, C^Cy-cycloalkyl, which in addition can contain an oxygen atom in the ring, aryl, C7-C2()-aralkyl C]-C2o-acyl, aroyl, Cj-C20-alkoxycarbonyl, C1-C20-alkylsulfonyl as well as arylsulfonyl can be cited. As alkyl-, silyl- and acyl radicals for the protective groups PG, especially the radicals that are known to one skilled in the art are considered. Preferred are the alkyl or silyl radicals that can be easily cleaved from the corresponding alkyl and silyl ethers, such as, for example, the methoxymethyl, methoxyethyl, ethoxyethyl, tetrahydropyranyl, tetrahydrofuranyl, trimethylsilyl, triethylsilyl, tert.-butyldimethylsilyl, tert.-butyldiphenylsilyl, tribenzylsilyl, triisopropylsilyl, benzyl, para-nitrobenzyl, and para-methoxybenzyl radicals, as well as alkylsulfonyl and arylsulfonyl radicals. As an alkoxycarbonyl radical, e.g., trichloroethyloxycarbonyl (Troc) is suitable. As an acyl radical, e.g., formyl, acetyl, propionyl, isopropionyl, trichloromethylcarbonyl, pivalyl, butyryl or benzoyl, which radical can be substituted with an amino and/or hydroxy group, is suitable. As amino protective groups PG, the radicals that are known to one skilled in the art are suitable. For example, the Alloc, Boc, Z, benzyl, f-Moc, Troc, stabase or benzostabase group can be mentioned. As halogen atoms, fluorine, chlorine, bromine or iodine can be considered. WO 2004/012735 10 PCT/EP2003/008483 The acyl groups can contain 1 to 20 carbon atoms, formyl, acetyl, propionyl, isopropionyl and pivalyl groups being preferred. The C2-Cio-alkylene-a,co-dioxy group that is possible for X is preferably an ethylene ketal or neopentyl ketal group. Preferred compounds of general formula I are those in which A-Y represents 0-C(=0) or NR.21-C(=0); D-E represents an H2C-CH2 group; G represents a CH2 group; Z represents an oxygen atom; R*a, R^b in each case represent (4-C10 alkyl or together a -(CH2)p group with p equal to 2 or 3 or 4; R^a R^b, independently of one another, represent hydrogen, Cj-Cio alkyl, C2-C10 alkenyl, or C2-C10 alkynyl; R3 represents hydrogen; R^a R^b, independently of one another, represent hydrogen or Ci-Cjo alkyl; R^ represents hydrogen, or C1-C4 alkyl or CH2OH or CH2NH2 or CH2N(alkyl, acyl) 1,2 or CH2Hal; R^ and R? together represent an additional bond or together an NH group or together an N-alkyl group or together a CH2 group or together an oxygen atom; W represents a group C(=X)R8 or a 2-methylbenzothiazol-5-yl radical or a 2-methylbenzoxazol-5-yl radical or a quinolin-7-yl radical or a 2-aminomethylbenzothiazol-5-yl radical or a 2-hydroxymethylbenzothiazol-5-yl radical or a 2-aminomethylbenzoxazol-5-yl radical or a 2-hydroxymethylbenzoxazol-5-yl radical; X represents a CR^R^ * group; R8 represents hydrogen or C1-C4 alkyl or a fluorine atom or a chlorine atom or a bromine atom; RlO/Rl 1 represent hydrogen/2-methylthiazol-4-yl or hydrogen/2-pyridyl or hydrogen/2-methyloxazol-4-yl or hydrogen/2-aminomethylthiazol-4-yl or hydrogen/2-aminomethyloxazol-4-yl or hydrogen/2-hydroxymethylthiazol-4-yl or hydrogen/2-hydroxymethyloxazol-4-yl. As linkers of general formula (III), compounds are preferred in which V represents a bond or an aryl radical, o is equal to zero, and T represents an oxygen atom. As linkers of general formula (III), in addition compounds are preferred in which V represents a bond or an aryl radical or a group NR24'-C(=0)-0-(CH2)S-^Q _ ; Q represents a bond or a group -0-C(=0)-NR2te—<f^ ; and o is 0 to 4. Especially preferred are compounds WO 2004/012735 PCT/EP2003/008483 11 of general formula (III), wherein V represents a bond or a group N R24b-C(=0)-0-(C H2)s-^~^ ; Q represents a bond or a group -0-C(=0)-NR24c ; o is equal to 0,2 or 3; s is equal to 1; and T is an oxygen atom. As linkers of general formula (IV), compounds are preferred in which o is zero to four, and q is zero to three. Especially preferred are compounds of general formula (IV), wherein o is 0,2 or 3; W1 is an oxygen atom; q is equal to 0; R22 is hydrogen, Ci -C3 alkyl or aralkyl; R23 is hydrogen or Ci -C3 alkyl; R24ais hydrogen or Cj -C3 alkyl; R27 is fluorine, chlorine, CN, NO2, CO2R28 or OR28; R28 is hydrogen or Ci -C5 alkyl; and U is oxygen, CHR22 or CHR22-NR23-C(=0)-. As recombinant proteins for use as recognition units, for example, binding regions derived from antibodies, so-called CDRs, are suitable. As framework structures for use as recognition units, for example, high-molecular structures that are not derived from antibodies are suitable. For example, structures of the fibronectin type 3 and of crystallins can be mentioned. As fragments of monoclonal antibodies for use as recognition units, for example, single-chain Fv, Fab, F(ab)2 as well as recombinant multimers can be mentioned. As preferred recognition units, those are considered that are suitable for, for example, the recognition and/or diagnosis and/or therapy of solid tumors and malignant diseases of the hematopoietic system. As recognition units that are additionally preferred, those are considered that allow a selective recognition of the disease-specific vascular system, preferably of the angiogenesis. Table 1 cites examples of especially preferred recognition units for treating solid tumors. WO 2004/012735 PCT/EP2003/008483 12 TABLE 1 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies leferences Gynecol. (GY) CA125' > 200 kD mucin GP OC 125 iCabawat et al., 1983; Szymendera, 1986 Ovarian 80 Kd GP OC 133 Vlasuko et al., Cancer Res, 1984 Ovarian 'SGA' 360 Kd GP OMI de Krester et al., 1986 Ovarian High Mr mucin Mo vl Miotti et al., Cancer Res, 1985 Ovarian High Mr mucin/ glycolipid Mo v2 Miotti et al., Cancer Res, 1985 Ovarian NS 3C2 Tsuji et al., Cancer Res, 1985 Ovarian NS 4C7 Tsuji et al., Cancer Res, 1985 Ovarian High Mr mucin ID3 Gangopadhyay et al., 1985 Ovarian High Mr mucin DU-PAN-2 Lan et al., 1985 GY 7700 KdGP F 36/22 Croghan et al., 1984 Ovarian *gp 68' 48 KdGP 4F7/7A10 Bhattacharya et al., 1984 GY 40,42kD GP OV-TL3 Poels et al., 1986 GY 'TAG-72' High Mr mucin B72.3 Thor et al., 1986 WO 2004/012735, 13 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Ovarian 300-400 KdGP df3 Kufe et al., 1984 Ovarian 60 KdGP 2C8/2F7 Bhattacharya et al., 1985 GY 105 KdGP MF 116 Mattes et al., 1984 Ovarian 38-40 kDGP Movl8 Miotti et al., 1987 GY •CEA* 180 KdGP CEA11-H5 Wagener et al., 1984 Ovarian CA 19-9 or GICA CA 19-9 (1116NS 19-9) Atkinson et al., 1982 Ovarian 'FLAP167 KdGP H17-E2 McDicken et al., 1985 Ovarian 72 Kd 791T/36 Perkins et al., 1985 Ovarian 69 KdPLAP NDOG2 Sunderland et al., 1984 Ovarian unknown Mr PLAP H317 Johnson et al., 1981 Ovarian pl85Hi±K2 4D5, 3H4,7C2, 6E9,2C4,7F3, 2H11,3E8,5B8, 7D3, SB8 Shepard et al., 1991 Uterus, Ovary HMFG-2 HMFG2 Epenetos et al., 1982 GY HMFG-2 3.14. A3 Burchell et al., 1983 Breast 330-450 KdGP DF3 Hayes etal., 1985 Breast NS NCRC-11 Ellis et al., 1984 Breast 37kD 3C6F9 Mandeville et al., 1987 Breast NS MBE6 Teramoto et al., 1982 Breast NS CLNH5 Glassy et al., 1983 WO 2004/012735 14 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Breast 47 KdGP MAC 40/43 Kjeldsen et al., 1986 Breast High Mr GP EMA Sloane et al., 1981 Breast High Mr GP HMFG1 HFMG2 Arklieetal., 1981 Breast NS 3.15.C3 Arklie et al., 1981 Breast NS M3, M8, M24 Foster etal., 1982 Breast 1 (Ma) Blood Group Ags Ml 8 Foster et al., 1984 Breast NS 67-D-ll Rasmussen et al., 1982 Breast Estrogen Receptor D547Sp, D75P3, H222 Kinsel et al., 1989 Breast EGF Receptor AntiEGF Sainsbury et al., 1985 Breast Laminine Receptor LR-3 Horan Hand et al., 1985 Breast erb B-2pl85 TA1 Gusterson et al., 1988 Breast NS H59 Hendler et al., 1981 Breast 126 KdGP 10-3D-2 Souleeta!., 1983 Breast NS HmABl,2 Imam et al., 1984; Schlometal., 1985 Breast NS MBR 1,2,3 Menard et al., 1983 Breast 95 Kd 24-17-1 Thompson et al., 1983 Breast 100 Kd 24-17-2 (3E1-2) Croghan et al., 1983 Breast NS F36/22.M7/105 Croghan et al., 1984 Breast 24 Kd Cll, G3,H7 Adams etal., 1983 WO 2004/012735 15 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Breast 90 KdGP B6-2 Colcher et al, 1981 Breast CEA& 180 KdGP Bl-1 Colcher et al., 1983 Breast Colon & pancreas, mucin-like Ca 19-9 Cam 17-1 Imperial Cancer Research Technology MAb listing Breast Milk mucin, nuclear protein SM3 Imperial Cancer Research Technology Mab listing Breast Milk mucin, nuclear protein SM4 Imperial Cancer Research Technology Mab listing Breast Affinity-purified milk mucin C-Mul (566) Imperial Cancer Research Technology Mab listing Breast P185hUiKZ 4D5 3H4,7C2, 6E9,2C4,7F3, 2H11,3E8,5B8, 7D3,5B8 Shepard et al., 1991 Breast CA 125 >200 KdGP OC 125 Kabawat et al., 1985 Breast High Mr mucin/ glycolipid MO v2 Miotti et al., 1985 Breast High Mr mucin DU-PAN-2 Lan et al., 1984 WO 2004/012735 16 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Breast ■gp48' 48 Kd GP 4F7/7A10 Bhattacharya et al., 1984 Breast 300-400 KdGP df3 Kufe et al., 1984 Breast 'TAG-72' high Mr mucin B72-3 Thor et al., 1986 Breast 'CEA'180 KdGP cccccCEA 11 Wagener et al., 1984 Breast 'PLAP* 67 Kd GP H17-E2 McDicken et al., 1985 Breast HMFG-2 >400 KdGP 3-14-A3 Burchell et al., 1983 Breast NS F023C5 Rivaetal., 1988 Colorectal TAG-72 HighMr mucin B72-3 Colcher et al., 1987 Colorectal GP37 (17-1A) 1038-17-1A Paul et al., 1986 Colorectal Surface GP C017-1A LoBuglio et al., 1988 1 Colorectal CEA ZCE-025 Pattetal., 1988 Colorectal CEA AB2 Griffin et al., 1988a Colorectal Cell surface AG HT-29-15 Cohnetal., 1987 Colorectal Secretory epithelium 250-30.6 Leydem et al., 1986 Colorectal Surface glycoprotein 44X14 Gallagher et al., 1986 Colorectal NS A7 Takahashi et al., 1988 Colorectal NS GA73-3 Munzetal., 1986 Colorectal NS 791T/36 Farrans et al., 1982 WO 2004/012735 17 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Colorectal Cell Membrane & Cytoplasmatic Ag 28A32 Smith et al., 1987 Colorectal CEA & Vindesin 28.19.8, Corvalen, 1987 Colorectal gp72 X MMCO-791 Byers et al., 1987 Colorectal high Mr mucin DU-PAN-2 Lanetal., 1985 Colorectal high Mr mucin ID3 Gangopadhyay et al., 1985 Colorectal CEA 180 KdGP CEA11-H5 Wagener et al., 1984 Colorectal 60 KdGP 2Cg/2F7 Bhattacharya et al., 1985 Colorectal CA-19-9 (or GICA) CA-19-9 (1116NS 19-9) Atkinson et al., 1982 Colorectal Lewis a PR5C5 Imperial Cancer Research Technology Mab Listing Colorectal Lewis a PR4D2 Imperial Cancer Research Technology Mab Listing Colorectal Colon mucus PR4D1 Imperial Cancer Research Technology Mab Listing Melanoma P97a 4-1 Woodbury et al., 1980 Melanoma P97a 8-2 M17 Brown, et al., 1981a WO 2004/012735 18 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Melanoma P97b 96-5 Brown, etal., 1981a Melanoma P97c 118-1,133-2, (113-2) Brown, etal., 1981a Melanoma P97c Ll> L10> R10 (Rl9) Brown etal., 1981b Melanoma P97d *12 Brown et al., 1981b Melanoma P97e k5 Brown et al., 1981b Melanoma P155 6-1 Loop et al., 1981 Melanoma Gj)3 disialogan-gliosides R24 Dippold et al., 1980 Melanoma P210, p60, p250 5-1 Loop et al., 1981 Melanoma P280 p440 225.28S Wilson et al., 1981 Melanoma GP 94,75,70&25 465.12S Wilson et al., 1981 Melanoma P240-P250, P450 9-2-27 Reisfeld et al., 1982 Melanoma 100,77,75 Kd Fll Chee et al., 1982 Melanoma 94 Kd 376.96S Imai et al., 1982 Melanoma 4 GP Chains 465.12S Imai et al., 1982; Wilson etal., 1981 Melanoma GP 74 15-75 Johnson & Reithmuller, 1982 Melanoma GP 49 15-95 Johnson & Reithmuller, 1982 WO 2004/012735 19 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Melanoma 230 Kd Mel-14 Carrel etal., 1982 Melanoma 92 Kd Mel-12 Carrel et al., 1982 Melanoma 70 Kd Me3-TB7 Carrel etal., 1:387,1982 Melanoma HMW MAA similar to 9-2-27 AG 225.28SD Kantor et al., 1982 Melanoma HMW MAA similar to 9-2-27 AG 763.24TS Kantoretal., 1982 Melanoma GP95 similar to 376-96S 465-12S 705F6 Stuhlmiller et al., 1982 Melanoma GP125 436910 Saxtonetal., 1982 Melanoma CD41 M148 Imperial Cancer Research Technology Mab listing Gastrointestinal (GO high Mr mucin ID3 Gangopadhyay et al., 1985 Gallbladder, Pancreas, Stomach high Mr mucin DU-PAN-2 Lanetal., 1985 Pancreas NS OV-TL3 Poels et al., 1984 Pancreas, Stomach, Esophagus 'TAG-72' high Mr mucin B72-3 Thoretal., 1986 WO 2004/012735 20 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Stomach 'CEA'180 KdGP CEA 11-H5 Wagener et al., 1984 Pancreas HMFG-2 > 400 KdGP 3-14-A3 Burchell et al., 1983 GI NS CCOLI Lemkin et al., 1984 Pancreas, Stomach CA 19-9 (or GICA) CA-19-9 (1116NS 19-9) and CA50 Szymendera, 1986 Pancreas CA125 GP OC125 Szymendera, 1986 Lung p185tti±K2 4D5, 3H4, 7C2, 6E9,2C4,7F3, 2H11,3E8,5B8, 7D3, SB8 Shepard et al., 1991 Non-small-cell lung cancer (NSCLC) NSCLC highMr mucin/glycolipid MO v2 Miotti et al., 1985 NSCLC 'TAG-72" highMr mucin B72-3 Thor et al., 1986 NSCLC High Mr mucin DU-PAN-2 Lan et al., 1985 NSCLC 'CEA' 180 kD GP CEA 11-H5 Wagener et al., 1984 Malignant Glioma Cytoplastic antigen that consists of 85HG-22 cells MUG 8-22 Stavrou, 1990 WO 2004/012735 21 PCT/EP2003/008483 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Malignant Glioma Cell surface Ag that consists of 85HGA63 cells MUC 2-63 Stavrou, 1990 Malignant Glioma Cell surface Ag that consists of 86HG-39 cells MUC 2-39 Stavrou, 1990 Malignant Glioma Cell surface Ag that consists of 86HG-39 cells MUG 7-39 Stavrou, 1990 Gl, Other P53 PAb 240, PAb 246, PAb 1801 Imperial Cancer Research Technology MaB Listing Small, Round-Cell Tumors Neural cell adhesion molecules ERIC-1 Imperial Cancer Research Technology MaB Listing Medulloblas-tomas, Neuroblastomas, Rhabdomyosarcomas M148 Imperial Cancer Research Technology MaB Listing WO 2004/012735 PCT/EP2003/008483 22 Tumor Antigen Identity/ Characteristics Monoclonal Antibodies References Neuroblastomas FMH25 Imperial Cancer Research Technology MaB Listing Kidneys & Glioblastomas P155 6-1 Loop et al., 1981 Bladders & Laryngeal Tumors "Ca Antigen" 350-390 kD CA1 Ashall et al., 1982 Neuroblastoma GD2 3F8 Cheung etal., 1986 Prostate Gp48 48 IcD GP 4F7/7A10 Bhattacharya et al., 1984 Prostate 60kDGP 2Cg/2F7 Bhattacharya et al., 1985 Thyroid 'CEA' 180kD GP CEA11-H5 Wagener et al., 1984 Prostata Neurocellin-2 (NC-2), TMEFF2, TENB2, tomoregulin, TMP-2 2H8,10G6 Berlex As especially preferred recognition units for treating hematological tumors, antibodies or antibody fragments, such as CD19, CD20, CD40, CD22, CD25, CD5, CD52, CD10, CD2, CD7, CD33, CD38, CD40, CD72, CD4, CD21, CD5, CD37 and 5 CD30, can also be mentioned. As especially preferred recognition units for anti-angiogenic therapy, antibodies or fragments thereof, such as VCAM, CD31, ELAM, endoglin, VEGFRI/II, avp3j Tie 1/2, TES23 (CD44ex6), phosphatidylserine, PSMA, VEGFR/VEGF complex or ED-B-fibronectin, can be mentioned. WO 2004/012735 PCT/EP2003/008483 23 The compounds that are mentioned below are especially preferred according to the invention as effector elements: (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S(E))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-thiazol-4-yl)-l-methyl-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R58S,9S,13Z,16S(E))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-methyl-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (1 S,3 S(E),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3 S(E),7S,1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-1 -methyl-vinyl] -8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3 S(E),7S,10R,11S, 12S, 16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l -methyl-vinyl]-?, 11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z, 16S(E))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-thiazol-4-yl)-l-methyl-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(E))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-methyl-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13 -tetramethyl-oxacyclohexadec-13 -ene-2,6-dione, (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3 S(E),7 S,10R,11S,12S,16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-l-methyl-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1.0]hepta-decane-5,9-dione, (lS,3S(E),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l-methyl-vinyl]-7,11 -dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1.0]hepta-decane-5,9-dione, WO 2004/012735 PCT/EP2003/008483 24 (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-fluoro-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-thiazol-4-yl)-l-fluoro-vinyl3-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-fluoro-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (1 S,3S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-8,8,10,12,16-pentamethyl-3-[1 -fluoro-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-l -fluoro-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione, (1S ,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l -fluoro-vinyl] -7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-chloro-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-thiazol-4-yl)-l -chloro-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S(Z))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-chloro-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pfentamethyl-3-[l-chloro-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3S(Z),7S,1 OR, 1 IS, 12S,16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-l-chloro-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo [14.1.0]heptadecane-5,9-dione, (lS,3S(Z),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l-chloro-vinyl]-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo [14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-[l -fluoro-2-(2-methyl-thiazol-4-yI)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, WO 2004/012735 PCT/EP2003/008483 25 (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-thiazol-4-yl)-1 -fluoro-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-fluoro-vinyl]-4,8-dih.ydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-fluoro-2-(2-methyl-thiazol-4-yl)-vinyl]-4517-dioxa-bicyclo [ 14.1.0]heptadecane-5,9-dione, (1S,3S(Z),7S,10R,11 S,12S,16R)-7,1 l-Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-l-fluoro-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione, (1 S,3S(Z),7S, 1 OR, 11S, 12S,16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l -fluoro-vinyl]-7,11 -dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione, (4S,7R,8S,9S, 13Z,16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-[l -chloro-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-thiazol-4-yl)-l-chloro-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-chloro-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1 S,3S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3 -[1 -chloro-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione, (1S,3S(Z),7S,10R,11S,12S,16R)-7,11 -Dihydroxy-3 -[2-(2-hydroxymethyl-thiazol-4-yl)-1 -chloro-vinyl]-10-ethyl-8,8,l 2,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1 .Ojhepta-decane-5,9-dione, (lS,3S(Z),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l-chloro-vinyl]-7,l 1 -dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,l 7-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione, (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-methyl-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-methyl-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, WO 2004/012735 PCT/EP2003/008483 26 (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-methyl-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13 -ene-2,6-dione, (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[ 1 -methyl-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[l -fluoro-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[1 -fluoro-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-chloro-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[ 1 -chloro-2-(2-pyridyl)-vinyl] -4,17-dioxa-bicyclo [14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-fluoro-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (1S,3S(Z),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetiame1hyl-3-[l-fluoro-2-(2-pyridyl)-vinyl]-4,l7-dioxa-bicyclo[l4.l.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-chloro-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (1S,3S(Z),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-chloro-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z,16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[l -methyl-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-yl)-l-methyl-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S(E))-16-[2-(2-Aminomethyl-oxazol-4-yl)-l -methyl-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-methyl-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, WO 2004/012735 PCT/EP2003/008483 27 (1 S,3 S(E),7S, 10R,11 S,12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-1 -methyl-vinyI]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo [14.1.0]heptadecane-5,9-dione, (lS,3S(E),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-l-methyl-vinyl]-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclof 14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-methyI-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-yl)-l-methyl-vinyl]-7-ethyI-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(E))-16-[2-(2-Aminomethyl-oxazol-4-yl)-l-methyl-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13 -ene-2,6-dione, (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-ethyl-8,8,12J16-tetramethyl-3- [ 1 -methyl-2-(2-methyl-oxazol-4-yl)-vinyl] -4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-l -methyl-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione, (lS,3S(E),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-l-methyl-vinyl] -7,11 -dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-fluoro-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-yl)-l-fluoro-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-oxazol-4-yl)-l-fluoro-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13 -ene-2,6-dione, (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-fluoro-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3S(Z),7S, 10R,11 S,12S, 16R)-7,1 l-Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-1 -fluoro-vinyl]-8,8,10,12,16-pentamethyl-4, i 7-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, WO 2004/012735 PCT/EP2003/008483 28 (lS,3S(Z),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-l-fluoro-vinyl]-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[ 1-chloro-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-oxazol-4-yl)-l-chloro-vinyl]-5,5j7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S(Z))-16-[2-(2-Aminomethyl-oxazol-4-yl)-l-chloro-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-chloro-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione, (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-1 -chloro-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-1 -chloro-vinyl]-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-fluoro-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-yl)-l-fluoro-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-oxazol-4-yl)-l-fluoro-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1S,3S(Z),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-fluoro-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3 S(Z),7S, 10R,11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-1 -fluoro-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione, (lS,3S(Z),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-l-fluoro-vinyl]-7,11 -dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1.0]hepta-decane-5,9-dione, § 0 • H "© \o § 0) 1 m T-H I •a I o *!> ^ O S t-—n t-H 1>» N .3 ^ ETj i—H -A of Ti o\ >i « 4 N f> •§ 00 ■a 1 $ i i cs I cs. I so y-H I £ Q I 00 I § *? <A in 1 § <s • F"< 1 1 § -a >> *<D <!f 3 ri PS 0 • r-( TD 1 43 £ £ <D I A 1 <N CO i—< <N i I m W, a o o CM lO <s o CO WO 2004/012735 PCT/EP2003/008483 30 (4S,7R,8S,9S,13Z,16S(E))-16-[2-(2-Aminomethyl-thiazol-4-yl)-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13 -tetramethyl-oxacyclohexadec-13 -ene-2,6-dione, (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3 -[2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3 S(E),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (lS,3S(E),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-vinyl]-7,11 -dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z, 16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione, (1 S,3 S(E),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-8,8,10,12,16-pentamethyl-3 -[2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[2-(2-pyridyl)-vinyl]-oxacycIohexadec-13-ene-2,6-dione, (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-5,5,7,9,13 -pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,ll-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, WO 2004/012735 PCT/EP2003/008483 31 (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec- 13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-ethyl~5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1 S,3S,7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-l 0-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3S,7S, 10R,11S, 12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,11-dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-propyl-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-7-propyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-propyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-propyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-propyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,ll-dihydroxy-10-propyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S ,9S, 13Z, 16S)-4,8-Dihydroxy-7-butyl-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yI)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-7-butyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, WO 2004/012735 PCT/EP2003/008483 32 (4S,7R,BS,9S, 13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-butyl-5,5,9,13 -tetramethyl-oxacyclohexadec- 13-ene-2,6-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-butyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-l 0-butyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,ll-dihydroxy-10-butyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-7-allyl-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy- 16-(2-hydroxymethyl-benzothiazol-5-yl)-7-allyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-allyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-allyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-allyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1,0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,ll-dihydroxy-10-allyl-8,8,12,16-tetramethyl-4,l 7-dioxa-bicyclo[14.1,0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-7-prop-2-inyl-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z, 16S)-4,8-Dihydroxy-l 6-(2-hydroxymethyl-benzothiazol-5-yl)-7-prop-2-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13 -ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-prop-2-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1S,3S,7S,1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-prop-2-inyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo [14.1.0]heptadecane-5,9-dione, WO 2004/012735 PCT/EP2003/008483 33 (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-prop-2-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,lIS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,ll-dihydroxy-10-prop-2-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo [14.1,0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-7-but-3 -enyl-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z, 16S)-4,8-Dihydroxy-l 6-(2-hydroxymethyl-benzothiazol-5-yl)-7-but-3-enyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-but-3-enyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-but-3-enyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-l 0-but-3-enyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,1 lS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,l 1-dihydroxy-10-but-3-enyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-7-but-3-inyl-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-l 6-(2-hydroxymethyl-benzothiazol-5-yl)-7-but-3-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13 -ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-but-3-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-but-3-inyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-but-3-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione, WO 2004/012735 PCT/EP2003/008483 34 (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,ll-dihydroxy-10-but-3-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-5,5,7,9,13-pentamethyI-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-5,5,7,9,13 -pentaraethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5 -yl)-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3S,7S, 1 OR, 11S, 12S, 16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-l 3-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1S,3S,7S,1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo [14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,l 1-dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-propyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoXazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, WO 2004/012735 PCT/EP2003/008483 35 (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-propyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-propyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1 S,3S,7S,1 OR, 11S, 12S, 16R)-7,1 l-Dihydroxy-10-propyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5 -yl)-4,17 -dioxa-bicyclo [14.1,0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-l 0-propyl-8,8,12,16-tetramethyl-4,l 7-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,ll-dihydroxy-10-propyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-butyl-5,5;9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-butyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-butyl-5,5,9,13 -tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-butyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.03heptadecane-5,9-dione, (1 S,3S,7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3 -(2-hydroxymethyl-benzoxazol-5-yl)-10-butyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,ll-dihydroxy- 10-butyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13ZJ16S)-4,8-Dihydroxy-7-allyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-allyl-5,5,9,13-tetramethyl-oxacyclohexadec-l 3 -ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-allyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, WO 2004/012735 PCT/EP2003/008483 36 (lS,3S,7S,10R,llS,12S,16R)-7,ll~Dihydroxy-10-allyl-8,8,12,16-tetraniethyl-3 -(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,11 -Dihydroxy-3 -(2-hydroxymethyl-benzoxazol-5 -yl)-10-aIlyI-8,8,12,16-tetramethyi-4,17-dioxa-bicyclo [14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,1 lS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,l 1-dihydroxy-10-allyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-prop-2-inyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13 -ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dih.ydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-prop-2-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S, 13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-prop-2-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (1 S,3S,7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-prop-2-inyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-10-prop-2-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,1 lS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,l 1-dihydroxy-10-prop-2-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-but-3-enyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-but-3-enyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-but-3-enyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-but-3-enyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, WO 2004/012735 PCT/EP2003/008483 37 (1S,3S,7S,10R,11S, 12S, 16R)-7,11 -Dihydroxy-3 -(2-hydroxymethyl-benzoxazol-5-yl)-10-but-3-enyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1S,3S,7S,10R,1 lS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,l 1-5 dihydroxy-10-but-3-enyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-7-but-3-inyl-5,5,9,13-tetramethyl-l 6-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-10 yl)-7 -but-3-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-l 3 -ene-2,6-dione, (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzoxazol-5-yI)-4,8-dihydroxy-7-but-3-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione, (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-but-3-inyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-15 dione, (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-l 0-but-3 -inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, (1 S,3S,7S, 1 OR, 11S, 12S, 16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,l 1 -20 dihydroxy-10-but-3-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione. In a compound of general formula (I) according to the invention that contains one of the above-mentioned elements, the hydrogen atoms in the above-mentioned * 1 3 elements are replaced in the positions indicated in formula (I) by radicals L -L , 25 wherein radicals L!-L3 have the above-indicated meanings. The invention also relates to linkers of general formula III1 RG1 (CH2)0—V—(CH2)—FG1 ||fl, in which RG1 can be an 0=C=N group or an S=C=N group, and o, V, q and FG* have 30 the meanings that are already mentioned above, as well as linkers of general formula III2 WO 2004/012735 PCT/EP2003/008483 38 RG2 (CHj)—V—(Cty—FG1 III2, in which RG2 can be a Hal-C(=T)-CHR22 group or a Hal-C(=T)-CHR22-NR23-C(=T) group or an R26-C(=0)-0-C(=T)-CHR22 group or an R2^-C(=0)-0-C(=T)-CHR22-5 NR23-C(=T) group; R2^ can be Cj-Cio alkyl aryl> or aralkyl, and o, V, q, T and FG* have the meanings that are already mentioned above, as well as linkers of general formula III RG3 <CH2)-V— (CHj)—FG1 Hp, in which 10 RG3 can be an OH group or an NHR24a group or a COOH group, and o, V, q and FGl have the meanings that are already mentioned above; but with the proviso that the compound l-(4-anuno-phenyl)-pyrrole-2,5-dione is not included. The invention also relates to linkers of general formula (IV1): R27 rg1— (ch2)—IV1 \=a(ch2)q—w2-c(=0)—u—(ch,)—fg1 15 s in which RG1 is an 0=C=N group or an S=C=N group, and o, q, r, W2, R27, U and FG1 have the meanings that are mentioned in claim 1; or linkers of general formula (IV2): 20 R27 rg2— wr-iv* x=a(ch2)q—wlc(=0)—u—(ch2)—fg1 in which WO 2004/012735 PCT/EP2003/008483 39 RG2 is aHal-C(=T)-CHR22 group or a Hal-C(=T)-CHR22-NR23-C(=T) group or anR26-C(=0)-0-C(=T)-CHR22 group or an R26-C(=0)-0-C(=T)-CHR22-NR23-C(=T) group, wherein R2^ is Cj-Cio alkyl, aryl, or aralkyl, and R22, R23, T, o, q, r, W2, R27, U and FG1 have the meanings that are mentioned in claim 1; 5 or linkers of general formula (IV ): r27 rg3— <ch2)0-/^ iv3 \==a(ch2) —wlc(=0)—u-(ch2)r— fg1 9 in which RG3 is an OH group or an NHR^4a group or a COOH group, and R24a, o, q, r, W2, R27, U and FG1 have the meanings that are mentioned in claim 1. • • 12 3 10 According to the invention, linkers of general formulas III, III or III are preferred, wherein V represents a bond or an aryl radical, o is equal to zero, and T is an oxygen atom. In addition, linkers of general formulas III1, IE2 or III3 according to the invention are preferred, in which V represents a bond or an aryl radical or a group nr!4b-c(=0)-0-(ch2) —_ 15 ^ ; Q represents a bond or a group -0-c(=0)-nr24c—<t^ — ;andois0to4. Especially preferred from the above are those linkers in which V represents a bond or a group nr24b-c(=0)-0-(ch2)s-^q _ Q ; Q represents a bond or a group -0-c(=0)-nr24'-^ ; o is equal to 0,2 or 3; sis equal to 1; and T is an 20 oxygen atom. In addition, preferred according to the invention are linkers of general formulas IV1, IV2 or IV3, in which o is zero to four and q is zero to three. Especially preferred from the above are those linkers in which o is 0,2 or 3; W1 is an oxygen atom; q is equal to 0; R22 is hydrogen, Q-C3 alkyl or aralkyl; R23 is hydrogen or C1-C3 alkyl; R24a WO 2004/012735 PCT/EP2003/008483 40 is hydrogen or C1-C3 alkyl; R27 is fluorine, chlorine, CN, NO2, CO2R28 or OR28; R28 is hydrogen or C1-C5 alkyl; and U is oxygen, CHR22 or CHR22-NR23-C(=0). Additionally, the invention relates to methods to react a linker of general formula III1 or IV1 with a compound of general 5 formula I, in which the condition that at least one group L*, L2 or L4 represent a linker need not be met, and in which and/or L2 and/or L4 have the meaning of a hydrogen atom, and free hydroxyl groups and/or amino groups that are not required for the reaction optionally are protected, to react a linker of general formula III2 or IV2 with a compound of general 10 formula I, in which the condition that at least one group L*, L2 or L4 represent a linker need not be met, and L* and/or L2 and/or L4 have the meaning of a hydrogen atom, and free hydroxyl groups and/or amino groups that are not required for the reaction are optionally protected, or to react a linker of general formula III3 or IV3 with a compound of general 15 formula I, in which the condition that at least one group L*, L2 or represent a linker need not be met, and L* and/or L2 and/or L4 have the meaning of a C(=0)Hal group or a C(=S)Hal group, and free hydroxyl groups and/or amino groups that are not required for the reaction are optionally protected. The invention also relates to the use of a compound of general formula I, 20 wherein the substituents have the above-mentioned meanings, but the condition that at least one substituent L1, L2 or L4 represents a linker of general formula III or IV need not be met, and at least one substituent L1, L2 or L4 represents hydrogen, a group C(=0)C1, or a group C(S)C1, in a method as described above. The invention also relates to the use of a compound of general formula I, 25 wherein the substituents have the above-mentioned meanings, but the condition that at least one substituent L1, L2 or L4 represent a linker of general formula III or IV need not be met, and at least one substituent L1, L2 or L4 represents hydrogen, a group C(=0)C1, or a group C(S)C1, for the production of an effector recognition unit conjugate as described above. 30 The invention also relates to the use of a linker of general formula III1, III2, III3, IV1, IV2 or IV3 for the production of an effector conjugate, as described above. WO 2004/012735 PCT/EP2003/008483 41 12 3 The invention also relates to the use of a linker of general formula III, III, III, IV1, IV2 or IV3 for the production of an effector recognition unit conjugate as described above. The invention also relates to the use of a recognition unit, as described above, in a process according to the invention for the production of an effector recognition unit conjugate, as described above. The invention also relates to the effector recognition unit conjugates according to the invention for use as a medicament or for the production of a medicament or a pharmaceutical composition. The invention relates finally to the use of the effector recognition unit conjugates according to the invention for the production of medicaments for the treatment of diseases that are associated with proliferative processes, such as tumors, inflammatory and/or neurodegenerative diseases, multiple sclerosis, Alzheimer's disease, or for the treatment of angiogenesis-associated diseases, such as tumor growth, rheumatoid arthritis or diseases of the ocular fundus. WO 2004/012735 PCT/EP2003/008483 42 Examples of the Synthesis of Linkers (L) Example LI (S) 2-[(3-Methyltrisulfanyl-propionyl)-methyl-amino]-propanoic acid 5 Example Lla (S) 2-[(3-Acetylsulfanyl-propionyl)-methyl-amino]-propanoic acid ethyl ester The solution of 15 g (89.5 mmol) of N-methylalanine ethyl ester-hydrochloride in 850 ml of anhydrous tetrahydrofuran is mixed at 23°C with 4.1 g of an 10 approximately 60% sodium hydride dispersion and, after 3 hours, with 23.5 g of 3-acetylsulfanyl-propanoic acid chloride. It is allowed to react for two days, mixed with saturated sodium bicarbonate solution, and extracted several times with ethyl acetate. The combined organic extracts are washed with saturated sodium chloride solution, dried over sodium sulfate, and the residue that is obtained after filtration and removal 15 of the solvent is purified by chromatography on fine silica gel. 17.6 g (67.3 mmol, 75%) of the title compound is isolated as a colorless oil. Example Lib (S) 2-[(3-Mercapto-propionyl)-methyl-amino]-propanoic acid 20 The solution of 17.6 g (67.3 mmol) of the compound prepared according to Example Lla in 150 ml of methanol is mixed at 23°C with 44 ml of a 5M sodium hydroxide solution, and it is stirred for 5 hours. By adding 4N hydrochloric acid, a pH of 2 is set, and it is extracted with dichloromethane. The combined organic extracts are washed with saturated sodium chloride solution and dried over sodium sulfate. 25 The residue that is obtained after filtration and removal of the solvent (13.0 g, maximum 67.3 mmol) is further reacted without purification. Example Lie (S) 2-[(3-Mercapto-propionyl)-methyl-amino]-propanoic acid methyl ester 30 The solution of 4.53 g (maximum 23.7 mol) of the crude product, prepared according to Example Lib, in 135 ml of diethyl ether is esterified at 0°C with an ethereal solution of diazomethane. After removal of the solvent, 4.59 g (22.4 mmol, WO 2004/012735 43 PCT/EP2003/008483 94%) of the title compound is isolated as a pale yellow oil, which is further reacted without purification. Example Lid 5 (S) 2-[(3-Methyltrisulfanyl-propionyl)-methyl-amino]-propanoic acid methyl ester The solution of 14 g (68.2 mmol) of the compound, prepared according to Example Lie, in 180 ml of trichloromethane is added to the solution of 21 g of 2-methyldisulfanyl-isoindole-l,3-dione in 420 ml of trichloromethane, and it is stirred for 16 hours at 23°C. It is concentrated by evaporation, dissolved in dichloromethane, 10 and stirred for 0.5 hour. Solid is filtered off, the filtrate is concentrated by evaporation, and the residue is purified by chromatography on fine silica gel. 16.2 g (57.2 mmol, 84%) of the title compound is isolated as a colorless oil. Example LI 15 (S) 2-[(3-Methyltrisulfanyl-propionyl)-methyl-amino]-propanoic acid The solution of 10 g (35.3 mmol) of the compound, prepared according to Example Lid, in 20 ml of ethanol is mixed with 11 of phosphate puffer with a pH of 7, pig liver esterase, and it is incubated at 27°C for 46 hours. By adding a 4N hydrochloric acid, the pH is adjusted to 1, it is extracted with dichloromethane, dried 20 over sodium sulfate, and after filtration and removal of the solvent, 8.3 g (30.8 mmol, 87%) of the title compound is isolated as a colorless oil, which is reacted without further purification. 1H-NMR (CDC13): 8 = 1.43+1.51 (3H), 2.55+2.63 (3H), 2.87 (2H), 2.88+3.00 (3H), 3.08-3.26 (2H), 4.63+5.19 (1H), 7.90 (1H) ppm. 25 Example L2 [(3-Methyltrisulfanyl-propionyl)-methyl-amino]-acetic acid Example L2a 30 2-[(3-Acetylsulfanyl-propionyl)-methyl-amino]-acetic acid ethyl ester 7.13 g (46.4 mmol) of N-methylglycine ethyl ester-hydrochloride is reacted analogously to Example Lla, and 6.9 g (27.9 mmol, 60%) of the title compound is isolated as a colorless oil. WO 2004/012735 44 PCT/EP2003/008483 Example L2b [(3-Mercapto-propionyl)-methyl-amino]-acetic acid 7.6 g (30.7 mmol) of the compound that is prepared according to Example L2a is reacted analogously to Example Lib, and 4.92 g (27.8 mmol, 90%) of the title compound is isolated as a colorless oil. Example L2c [(3-Mercapto-propionyl)-methyl-amino]-acetic acid methyl ester 4.92 g (27.8 mmol) of the compound that is prepared according to Example L2b is reacted analogously to Example Lie, and 5.01 g (26.2 mmol, 94%) of the title compound is isolated as a colorless oil. Example L2d [(3-Methyltrisulfanyl-propionyl)-methyl-amino]-acetic acid methyl ester 2.00 g (10.5 mmol) of the compound that is prepared according to Example L2c is reacted analogously to Example Lid, and 2.33 g (8.65 mmol, 82%) of the title compound is isolated as a colorless oil. Example L2 [(3-Methyltrisulfanyl-propionyl)-methyl-amino]-acetic acid 2.00 g (7.83 mmol) of the compound that is prepared according to Example L2d is reacted analogously to Example LI, and 0.64 g (2.51 mmol, 32%) of the title compound is isolated as a colorless oil. *H-NMR (CDC13): 8 = 2.41+2.56 (3H), 2.61-3.27 (7H), 3.98 (2H), 4.38 (1H) ppm. Example L3 (S) 2-[(3-Methyltrisulfanyl-propionyl)-methyl-amino]-3-phenyl-propionicacid WO 2004/012735 45 PCT/EP2003/008483 Example L3a (S) 2-[(3-Acetylsulfanyl-propionyl)-methyl-ammo]-3-phenyl-propanoic acid ethyl ester 7.73 g (31.7 mmol) of N-methylphenylalanine ethyl ester-hydrochloride is reacted analogously to Example Lla, and 2.3 g (6.82 mmol, 22%) of the title compound is isolated as a colorless oil. Example L3b (S) 2-[(3-Mercapto-propionyl)-methyl-amino]-3-phenyl-propanoic acid 1.09 g (3.23 mmol) of the compound that is prepared according to Example L3a is reacted analogously to Example Lib, and 0.744 g (2.78 mmol, 86%) of the title compound is isolated as a colorless oil. Example L3c (S) 2-[(3-Mercapto-propionyl)-methyl-amino]-3-phenyl-propanoic acid methyl ester 0.74 g (2.77 mmol) of the compound that is prepared according to Example L3b is reacted analogously to Example Lie, and 0.77 g (2.74 mmol, 99%) of the title compound is isolated as a colorless oil. Example L3d (S) 2-[(3-MethyltrisulfanyI-propionyl)-methyl-amino]-3-phenyl-propanoic acid methyl ester 0.77 g (2.74 mmol) of the compound that is prepared according to Example L3c is reacted analogously to Example Lid, and 0.72 g (2.00 mmol, 73%) of the title compound is isolated as a colorless oil. Example L3 (S)2-[(3-Methyltrisulfanyl-propionyl)-methyl-amino]-3-phenyl-propanoicacid 0.72 g (2.00 mmol) of the compound that is prepared according to Example L3d is reacted analogously to Example LI, and 0.49 g (1.42 mmol, 71%) of the title compound is isolated as a colorless oil. Example L4 WO 2004/012735 46 PCT/EP2003/008483 4-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-butanoic acid 20.0 g (193.9 mmol) of 4-aminobutyric acid is mixed with 19 g of maleic acid anhydride, 290 ml of acetic acid, and it is heated for 4 hours in an oil bath at 130°C. It is azeotropically concentrated by evaporation with repeated addition of toluene, the residue is dissolved in dichloromethane and purified by chromatography on fine silica gel. 17.1 g (93.4 mmol, 48%) of the title compound is isolated as a crystalline solid. 1H-NMR (CDC13): 8 = 1.93 (2H), 2.38 (2H), 3.60 (2H), 6.71 (2H) ppm. Example L4a l-(3-Isocyanato-propyl)-pyrrole-2,5-dione 5.0 g (27.3 mmol) of the compound that is prepared according to Example L4 is dissolved in 90 ml of tetrahydrofuran, mixed with 8 ml of triethylamine and 6.17 ml of phosphoric acid diphenylester azide, and it is stirred for 1.5 hours at 23 °C. Then, it is mixed with 110 ml of toluene, the tetrahydrofuran is distilled off, and it is heated for 2 hours to 70°C. The crude product is purified by chromatography on fine silica gel. 1.77 g (9.82 mmol, 36%) of the title compound is isolated. Example L5 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 100 g (762 mmol) of 6-aminocaproic acid is reacted analogously to Example L5, and 93.8 g (444 mmol, 58%) of the title compound is isolated as a crystalline solid. iH-NMR (CDCI3): 8 = 1.34 (2H), 1.55-1.70 (4H), 2.34 (2H), 3.51 (2H), 6.69 (2H) ppm. Example L5a l-(5-Isocyanato-pentyl)-pyrrole-2,5-dione 10.0 g (47.3 mmol) of the compound that is prepared according to Example L5 is reacted analogously to Example L4a, and 3.19 g (15.3 mmol, 32%) of the title compound is isolated as a colorless oil. Example L6 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid WO 2004/012735 47 PCT/EP2003/008483 10 g (49.7 mmol) of 11-aminoundecanoic acid is reacted analogously to Example L5, and 6.29 g (22.4 mmol, 45%) of the title compound is isolated as a crystalline solid. iH-NMR (CDC13): 8 = 1.19-1.36 (12H), 1.51-1.67 (4H), 2.34 (2H), 3.49 (2H), 6.68 (2H) ppm. Example L6a 1 -(10-Isocyanato-decyl)-pyrrole-2,5-dione 5.28 g (18.8 mmol) of the compound that is prepared according to Example L6 is reacted analogously to Example L4a, and 3.37 g (12.1 mmol, 64%) of the title compound is isolated as a colorless oil. Example L7 1 -(4-Amino-phenyl)-pyrrole-2,5-dione The solution of 21.6 g (200 mmol) of 1,4-phenylenediamine in 200 ml of tetrahydrofuran is mixed over 1.5 hours with the solution of 19.6 g of maleic acid anhydride, and it is stirred for 22 hours at 23°C. It is filtered, rewashed with tetrahydrofuran, and the filtrate is dried. 37.1 g (197 mmol, 98%) of the title compound is isolated as a crystalline solid. iH-NMR (d6-DMSO): 8 = 6.28 (1H), 6.48 (1H), 6.53 (2H), 7.30 (2H), 7.50-9.00 (2H) ppm. Example L8 l-(4-Hydroxy-phenyl)-pyrrole-2,5-dione The suspension that consists of 5.0 g (45.8 mmol) of 4-aminophenol, 4.49 g of maleic acid anhydride and 40 ml of acetic acid is refluxed for 3 hours. It is concentrated by evaporation, residual acetic acid is removed azeotropically by repeated distillation with acetic acid, and the residue is purified by chromatography on fine silica gel. 2.83 g (15.0 mmol, 33%) of the title compound is isolated. 1H-NMR (d6-DMSO): 8 = 6.83 (2H), 7.09 (2H), 7.13 (2H), 9.71 (1H) ppm. Example L9 WO 2004/012735 48 PCT/EP2003/008483 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid4-hydroxyraethyl-2-nitro-phenyl ester The solution of 5.0 g (29.6 mmol) of 4-hydroxymethyl-2-nitro-phenol in 250 ml of dichloromethane is mixed with 6.1 g of N,N'-dicyclohexylcarbodiimide and 2.4 ml of pyridine, and the solution of 5.5 g of the compound, prepared according to Example L4, in 250 ml of dichloromethane, is added dropwise within 15 minutes. It is stirred for one more hour at 23 °C, filtered, the filtrate is concentrated by evaporation and purified by chromatography on fine silica gel. 1.73 g (5.2 mmol, 18%) of the title compound is isolated. 1H-NMR (CDCI3): 8 = 2.07 (3H), 2.67 (2H), 3.67 (2H), 4.79 (2H), 6.72 (2H), 7.28 (1H), 7.66 (1H), 8.10 (1H) ppm. Example L10 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid4-hydroxymethyl-2-nitro-phenyl ester Analogously to Example L9,5.0 g (29.6 mmol) of 4-hydroxymethyl-2-nitro-phenol is reacted with 6.34 g of the compound that is prepared according to Example L5, and after working-up and purification, 3.78 g (10.4 mmol, 35%) of the title compound is isolated. !H-NMR (CDCI3): 8 = 1.42 (2H), 1.66 (2H), 1.88 (2H), 2.64 (2H), 3.55 (2H), 4.78 (2H), 6.69 (2H), 7.21 (1H), 7.64 (1H), 8.09 (1H) ppm. Example LI 1 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-hydroxymethyl-2-nitro-phenyl ester Analogously to Example L9,5.0 g (29.6 mmol) of 4-hydroxymethyl-2-nitro-phenol is reacted with 8.44 g of the compound that is prepared according to Example L6, and after working-up and purification, 3.78 g (10.4 mmol, 35%) of the title compound is isolated. 1H-NMR (CDCI3): 8 = 1.21-1.63 (14H), 1.76 (2H), 1.99 (1H), 2.63 (2H), 3.51 (2H), 4.78 (2H), 6.68 (2H), 7.21 (1H), 7.65 (1H), 8.10 (1H) ppm. Example LI 2 WO 2004/012735 PCT/EP2003/008483 49 4-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-butanoic acid 4-hydroxymethyl-phenyl ester 5.5 g (23,1 mmol) 4-tert-Butyldimethylsilanyloxymethyl-phenol, 20 mg N,N-Dimethyl-4-aminopyridine und 4.23 g (23,1 mmol) of the compound prepared according to Example L4 are dissolved in 92 ml of dichloromethane and cooled to 5 0°C. 4.77 g (23.1 mmol) N,N'-Dicyclohexylcarbodiimide in 24 ml dichloromethane are added dropwise to the cooled solution over a period of 15 min. The mixture is stirred for 16 hours at 23 °C, filtered, the filtrate is concentrated and purified by chromatography on fine silica gel. 7.18 g (17.8 mmol, 77%) 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid-4-tert-butyldimethylsilanyloxymethyl-phenyl ester are 10 isolated. 1.42 g thereof are dissolved in 63 ml THF and 7 ml water, and 0.67g (3.52 mmol) p-toluenesulfonic acid are added at room temperature. After 16 hours, a saturated sodium bicarbonate solution is added and the mixture is extracted several times with ethyl acetate. The combined organic layers are washed with a saturated solution of sodium chloride, dried over sodium sulfate and purified by chromatography 15 on fine silica gel. 0.43 g (1.5 mmol, 42%) of the title compound are isolated. *H-NMR (CDCI3): 8 = 1.71 (1H), 2.04 (2H), 2.58 (2H), 3.67 (2H), 4.68 (2H), 6.71 (2H), 7.09 (2H), 7.38 (2H) ppm. Example LI 3 20 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l -yl)-hexanoic acid 4-hydroxymethyl-phenyl ester Analogously to Example L12, 4.02 g (13.8 mmol) 4-tert-butyldimethylsilanyloxymethyl- phenol are reacted with 3.56 g (13.8 mmol) of the compound prepared according to Example L5. After working-up, purification and analogous treatment with p-toluenesulfonic acid, 3,19 g (10.1 mmol, 60%) of the title 25 compound are isolated. 'H-NMR (CDCI3): 8 = 1.42 (2H), 1.59-1.83 (5H), 2.55 (2H), 3.55 (2H), 4.68 (2H), 6.69 (2H), 7.06 (2H), 7.38 (2H) ppm. Example LI 4 30 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-hydroxymethyl-phenyl ester Analogously to Example L12, 5.41 g (22.7 mmol) 4-tert-butyldimethylsilanyloxymethyl- phenol are reacted with 6.39 g (22.7 mmol) of the WO 2004/012735 50 PCT/EP2003/008483 compound prepared according to Example L6. After working-up, purification and analogous treatment with p-toluenesulfonic acid, 5.91 g (15.3 mmol, 67%) of the title compound are isolated. 'H-NMR (CDCla): 8 = 1.24-1.43 (12H), 1.57 (3H), 1.74 (2H), 2.55 (2H), 3.50 (2H), 4.69 (2H), 6.68 (2H), 7.06 (2H), 7.38 (2H) ppm. Example LI 5 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid4-hydroxymethyl-2-chloro-phenyl ester Analogously to Example L9, 5.0 g (29.6 mmol) of 4-hydroxymethyl-2-chloro-phenol are reacted with 5.42 g of the compound prepared according to Example L4. After working-up and purification, 8.49 g (26.2 mmol, 89%) of the title compound are isolated. JH-NMR (CDC13): 8 = 2.07 (3H), 2.64 (2H), 3.67 (2H), 4.67 (2H), 6.72 (2H), 7.14 (1H), 7.27 (1H), 7.46 (1H) ppm. Example L16 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoicacid4-hydroxymethyl-2-chloro-phenyl ester Analogously to Example L9, 5.0 g (29.6 mmol) of 4-hydroxymethyl-2-chloro-phenol are reacted with 6.24 g of the compound prepared according to Example L5. After working-up and purification, 5.11 g (14.5 mmol, 49%) of the title compound are isolated. lH-NMR (CDCI3): 8 = 1.43 (2H), 1.66 (2H), 1.81 (3H), 2.61 (2H), 3.55 (2H), 4.67 (2H), 6.69 (2H), 7.10 (1H), 7.26 (1H), 7.46 (1H) ppm.' Example LI7 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-hydroxymethyl-2-chloro-phenyl ester Analogously to Example L9, 4.61 g (29 mmol) 4-hydroxymethyl-2-chloro-phenol are reacted with 8.17 g of the compound prepared according to Example L6. After working-up and purification, 4.61 g (10.9 mmol, 38%) of the title compound are isolated. WO 2004/012735 51 PCT/EP2003/008483 'H-NMR (CDCI3): 8= 1.18-1.84 (17H), 2.61 (2H), 3.51 (2H), 4.67 (2H), 6.68 (2H), 7.10 (IE), 7.27 (1H), 7.46 (1H) ppm. Example LI 8 5 l-(6-Hydroxy-hexyl)-pyrrol-2,5-dione 26 ml of a 1,0M solution of borane-tetrahydrofurane-complex in tetrahydrofurane is added to a solution of 5.0 g (23.7 mmol) of the acid prepared according to Example L5 in 50 ml of anhydrous tetrahydrofurane and the mixture is stirred for 3 hours at 23°C. The mixture is poured into a saturated solution of sodium bicarbonate, extracted 10 several times with ethyl acetate, and the combined organic extracts are dried over sodium sulfate. After filtration and removal of the solvent, the residue is purified by chromatography. 2.53 g (12.8 mmol, 54%) of the title compound are isolated. !H-NMR (CDCI3): 8= 1.24-1.65 (9H), 3.52 (2H), 3.63 (2H), 6.68 (2H) ppm. 15 WO 2004/012735 52 PCT/EP2003/008483 Examples of the Synthesis of Effector-Linker Conjugates (EL) Example ELI (4S,7R,8S,9S,13Z,16S)-[3-(2,5-Dioxo-2,5-dihydro-pyrroI-l-yl)-propyl]-carbamicacid-5 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester Example ELI a (4S,7R,8S,9S,13Z,16S)-7-AUyl-8-(te^butyl-dimethyl-silanyloxy)-4-hydroxy-10 5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5 -yl)-oxacyclohexadec-13 -ene-2,6-dione The solution of 6.0 g (7.93 mmol) of (4S,7R,8S,9S,13Z,16S)-7-allyl-4,8-bis(/er/-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, which was produced analogously to the 15 process that is described in WO 00/66589, in 186 ml of anhydrous dichloromethane is mixed at 0°C with 26.4 ml of a 20% solution of trifluoroacetic acid in dichloromethane, and it is stirred for 6 hours at 0°C. It is poured into saturated sodium bicarbonate solution, extracted with dichloromethane, the combined organic extracts are washed with water and dried over magnesium sulfate. The residue that is obtained 20 after filtration and removal of the solvent is purified by chromatography on fine silica gel. 3.32 g (5.17 mmol, 65%) of the title compound is isolated as a colorless solid. 1H-NMR (CDC13): 5 = 0.09 (3H), 0.12 (3H), 0.93 (9H), 1.00 (3H), 1.06 (3H), 1.22 (3H), 1.70 (3H), 1.03-1.77 (5H), 1.95 (1H), 2.31-2.56 (6H), 2.83 (3H), 2.87 (1H), 3.00 (1H), 3.30 (1H), 3.90 (1H), 4.09 (1H), 4.94-5.03 (2H), 5.20 (1H), 5.77 (1H), 5.88 25 (1H), 7.34 (1H), 7.78 (1H), 7.95 (1H) ppm. Example ELlb (4S,7R,8S,9S,13Z,16S)-3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]-carbamicacid-7-allyl-8-/er/-butyl-dimethylsilyloxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-30 5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 50 mg (78 |imol) of the compound that is prepared according to Example EL la is dissolved in a mixture of 1.5 ml of trichloromethane and 1.5 ml of dimethylformamide, mixed with 144 mg of the linker that is prepared according to WO 2004/012735 53 PCT/EP2003/008483 Example L4a, 79 mg of copper(I) chloride, and it is heated for 18 hours to 70°C. The crude mixture is purified by chromatography on thin-layer plates, and 51 mg (62 jamol, 80%) of the title compound is isolated as a colorless oil. 5 Example ELI (4S,7R,8S,9S,13Z,16S)-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]-carbamicacid-7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester The solution of 41 mg (50 |imol) of the compound, prepared according to 10 Example lb, in a mixture of 0.8 ml of tetrahydrofuran and 0.8 ml of acetonitrile is mixed with 310 jul of hexafluorosilicic acid, 310 pi of hydrogen fluoride-pyridine complex, and it is stirred for 23 hours at 23°C. It is poured into a 5% sodium hydroxide solution, extracted with ethyl acetate, the combined organic extracts are washed with a saturated sodium chloride solution and dried over sodium sulfate. The 15 residue that is obtained after filtration and removal of the solvent is purified by chromatography on thin-layer plates, and 26 mg (36.7 [imol, 73%) of the title compound is isolated as a colorless foam. *H-NMR (CDC13): 5 = 0.99 (3H), 1.14 (3H), 1.17 (3H), 1.20-1.51 (3H), 1.54-1.87 (6H), 1.70 (3H), 2.22 (1H), 2.28-3.02 (9H), 2.83 (3H), 3.31 (1H), 3.45 (1H), 3.68 20 (1H), 4.44+4.83 (1H), 4.99 (1H), 5.03 (1H), 5.15 (1H), 5.61 (1H), 5.72 (1H), 5.91 (1H), 6.68 (2H), 7.36 (1H), 7.78 (1H), 7.90 (1H) ppm. Example EL2 (lS,3S,7S,10R,llS,12S,16R)-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]-25 carbamic acid-10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-7-yl ester (A) and (lR,3S,7S,10R,llS,12S,16S)-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]~ carbamic acid-10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-7-yl ester (B) 30 The solution of 44 mg (62.2 pmol) of the compound, prepared according to Example 1, in 2.0 ml of dichloromethane is cooled to -50°C and mixed in portions over a period of 1.5 hours with a total of 1.7 ml of an approximately 0.1 M solution of dimethyl dioxiran in acetone. It is poured into a saturated sodium thiosulfate solution, WO 2004/012735 54 PCT/EP2003/008483 extracted with dichloromethane, and the combined organic extracts are dried over sodium sulfate. The residue that is obtained after filtration and removal of the solvent is purified by chromatography on thin-layer plates, and 22.7 mg (31.4 [imol, 50%) of title compound A as well as 7.6 mg (10.5 (imol, 17%) of title compound B are isolated in each case as a colorless foam. iH-NMR (CDC13) of A: 8 = 1.01 (3H), 1.14 (3H), 1.16 (3H), 1.20-1.94 (8H), 1.32 (3H), 2.11-2.74 (9H), 2.82 (1H), 2.84 (3H), 3.30 (2H), 3.48 (2H), 3.68 (1H), 4.36+4.93 (1H), 4.99 (1H), 5.04 (1H), 5.54 (1H), 5.69 (1H), 6.05 (1H), 6.68 (2H), 7.32 (1H), 7.80 (1H), 7.88 (1H) ppm. iH-NMR (CDCI3) of B: 8 = 1.02 (6H), 1.26 (3H), 1.33 (1H), 1.23-2.27 (12H), 2.54-2.78 (4H), 2.82 (3H), 2.91 (1H), 3.13 (1H), 3.40 (2H), 3.66 (1H), 4.11 (1H), 4.84 (1H), 4.95 (1H), 5.01 (1H), 5.70 (1H), 5.81+5.93 (1H), 6.04+6.13 (1H), 6.69 (2H), 7.35 (1H), 7.75 (1H), 7.90+7.99 (1H) ppm. Example EL3 (4S,7R,8S,9S,13Z,16S)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-pentyl]-carbamicacid-7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester Example EL3a (4S,7R,8S,9S,13Z,16S)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-pentyl]-carbamicacid-7-allyl-8-?m-butyl-dimethylsilyloxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-4-yl ester 50 mg (78 jxmol) of the compound that is prepared according to Example EL la is reacted analogously to Example ELlb with the linker that is produced according to Example L5a, and after purification, 39 mg (45.9 jumol, 59%) of the title compound is isolated as a colorless oil. Example EL3 (4S,7R,8S,9S,13Z,16S)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-pentyl]-carbamicacid-7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester WO 2004/012735 55. PCT/EP2003/008483 84 mg (98.8 |a.mol) of the compound that is prepared according to Example EL3a is reacted analogously to Example ELI, and after purification, 43 mg (58.4 jimol, 59%) of the title compound is isolated as a colorless foam. iH-NMR (CDC13): 6 = 0.89 (3H), 0.96 (3H), 0.85-1.97 (17H), 1.12 (3H), 2.16-3.01 (10H), 2.82 (3H), 3.44 (IH), 3.65 (IH), 4.41+4.53 (IH), 4.98 (IH), 5.03 (IH), 5.15 (IH), 5.60 (IH), 5.71 (IH), 5.90 (IH), 6.68 (2H), 7.35 (IH), 7.77 (IH), 7.89+7.96 (IH) ppm. Example EL4 (1 S,3S,7S, 1 OR, 11S, 12S, 16R)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-pentyl3-carbamic acid-10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-7-yl ester (A) and (1 R,3 S,7S, 1 OR, 11S, 12S, 16S)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-pentyl]-carbamic acid-10-allyl-l 1 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-7-yl ester (B) 26 mg (35.3 nmol) of the compound that is prepared according to Example EL3 is reacted analogously to Example EL2, and after purification, 9.1 mg (12.1 ^imol, 34%) of title compound A as well as 3.0 mg (4.0 jimol, 11%) of title compound B are isolated in each case as a colorless foam. iH-NMR (CDCI3) of A: 8 = 0.83-1.94 (15H), 0.98 (3H), 1.14 (3H), 1.16 (3H), 1.32 (3H), 2.15-2.82 (8H), 2.84 (3H), 3.44 (2H), 3.51 (IH), 3.66 (IH), 4.46 (IH), 4.99 (IH), 5.04 (IH), 5.54 (IH), 5.69 (IH), 6.06 (IH), 6.68 (2H), 7.33 (IH), 7.80 (IH), 7.89 (IH) ppm. iH-NMR (CDCI3) of B: 8 = 0.78-2.74 (23H), 1.01 (3H), 1.03 (3H), 1.33 (3H), 2.82 (3H), 2.91 (IH), 3.14 (IH), 3.39 (IH), 3.47 (2H), 3.67 (IH), 4.12 (IH), 4.49 (IH), 4.92-5.06 (2H), 5.53+5.80 (IH), 5.69 (IH), 6.11 (IH), 6.68 (2H), 7.34 (IH), 7.74+7.79 (IH), 7.89+8.02 (IH) ppm. Example EL5 (4S,7R,8S,9S,13Z,16S)-[10-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-decyl]-carbamic acid-7-allyl-8 -hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester WO 2004/012735 56 PCT/EP2003/008483 Example EL5a (4S,7R,8S,9S,13Z,16S)-[10-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-decyl]-carbamic acid-7-allyl-8 -te^butyl-dimethylsilyloxy- 5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 50 mg (78 nmol) of the compound that is prepared according to Example ELla is reacted analogously to Example EL lb with the linker that is produced according to Example L6a, and after purification, 56 mg (60.8 (imol, 78%) of the title compound is isolated as a colorless oil. Example EL5 (4S,7R,8S,9S,13Z,16S)-[10-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-decyl]-carbamic acid-7-allyl-8 -hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 20 mg (21.7 nmol) of the compound that is prepared according to Example EL5a is reacted analogously to Example ELI, and after purification, 10 mg (12.4 jimol, 57%) of the title compound is isolated as a colorless foam. lH-NMR(CDCl3): 5 = 0.91-1.87 (22H), 0.97 (3H), 1.13 (3H), 1.17 (3H), 1.70 (3H), 2.18-2.69 (8H), 2.80 (IH), 2.82 (3H), 2.96 (IH), 3.47 (IH), 3.50 (2H), 3.66 (IH), 3.97+4.36 (IH), 4.98 (IH), 5.04 (IH), 5.16 (IH), 5.61 (IH), 5.72 (IH), 5.91 (IH), 6.68 (2H), 7.37 (IH), 7.77 (IH), 7.90+7.97 (lH)ppm. Example EL6 (1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-[10-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-decyl]-carbamic acid-10-allyl-l 1 -hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-7-yl ester (A) and (lR,3S,7S,10R,llS,12S,16S)-[10-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-decyl]-carbamic acid-10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-7-yl ester (B) 18 mg (22 jLimol) of the compound that is prepared according to Example EL5 is reacted analogously to Example EL2, and after purification, 9.2 mg (11.2 pimol, 51%) of title compound A as well as 3.2 mg (3.9 jimol, 18%) of title compound B are isolated in each case as a colorless foam. WO 2004/012735 57 PCT/EP2003/008483 iH-NMR (CDCI3) of A: 8 = 0.98 (3H), 1.14 (3H), 1.16 (3H)S 1.32 (3H), 1.03-1.67 (21H), 1.71-1.94 (3H), 2.18-2.78 (9H), 2.83 (3H), 3.50 (3H), 3.66 (IH), 3.87+4.43 (IH), 4.98 (IH), 5.04 (IH), 5.53 (IH), 5.69 (IH), 6.07 (IH), 6.68 (2H), 7.33 (IH), 7.80 (IH), 7.89+7.93 (IH) ppm. iH-NMR (CDCI3) of B: 8 = 0.80-1.64 (21H), 1.01 (3H), 1.03 (3H), 1.25 (3H), 1.33 (3H), 1.79-2.25 (5H), 2.34+3.14 (IH), 2.52-2.76 (4H), 2.81 (3H), 2.91 (IH), 3.40 (IH), 3.51 (2H), 3.67+3.82 (IH), 4.13+4.26 (IH), 4.46 (IH), 4.94 (IH), 5.01 (IH), 5.70 (IH), 5.81+5.94 (IH), 6.05+6.12 (IH), 6.68 (2H), 7.36 (IH), 7.74 (IH), 7.91+8.02 (IH) ppm. Example EL7 (4S,7R,8S,9S,13Z,16S)-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]-carbamic acid-7-allyl-4-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5 -yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester Example EL7a (4S,7R,8S,9S, 13Z,16S)-7-Allyl-4-(te^butyl-dimethyl-silanyloxy)-8-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-l 3-ene-2,6-dione The solution of 5.3 g (7.01 mmol) of (4S,7R,8S,9S,13Z,16S)-7-allyl-4,8-bis(fe?t-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione, which was produced analogously to the process described in WO 00/66589, in a mixture of 85 ml of tetrahydrofuran and 85 ml of acetonitrile, is mixed with 31.7 ml of hexafluorosilicic acid, cooled to 0°C, 8.1 ml of trifluoroacetic acid is added dropwise, and it is stirred for 20 hours at 0°C. It is poured into water, neutralized by adding a saturated sodium bicarbonate solution and extracted several times with ethyl acetate. The combined organic extracts are washed with saturated sodium chloride solution, dried over sodium sulfate, and the residue that is obtained after filtration and removal of the solvent is purified by chromatography on fine silica gel. 2.82 g (4.39 mmol, 63%) of the title compound is isolated as a colorless solid. iH-NMR (CDCI3): 8 = -0.09 (3H), 0.08 (3H), 0.84 (9H), 1.08 (3H), 1.10 (3H), 1.12 (3H), 1.21-1.86 (5FI), 1.70 (3H), 2.15 (IH), 2.29-2.97 (8H), 2.84 (3H), 3.14 (IH), WO 2004/012735 58 PCT/EP2003/008483 3.96 (IH), 4.03 (IH), 4.97-5.06 (2H), 5.23 (IH), 5.61 (IH), 5.77 (IH), 7.35 (IH), 7.79 (IH), 7.93 (lH)ppm. Example EL7b (4S,7R,8S,9S,13Z,16S)-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]-carbamicacid-7-allyl-4-/er/-butyl-dimethylsilyloxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 100 mg (156 |imol) of the compound that is prepared according to Example EL7a is reacted analogously to Example ELlb with the linker that is produced according to Example L4a, and after purification, 121 mg (147 jamol, 94%) of the title compound is isolated as a colorless oil. Example EL7 (4S,7R,8S,9S,13Z,16S)-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]-carbamicacid-7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 46 mg (56 |Amol) of the compound that is prepared according to Example EL7b is reacted analogously to Example ELI, and after purification, 17 mg (24 jimol, 43%) of the title compound is isolated as a colorless foam. *H-NMR (CDC13): 8 = 0.99-1.30 (2H), 1.03 (3H), 1.07 (3H), 1.21 (3H), 1.51- 1.97 (6H), 1.72 (3H), 2.27-2.61 (6H), 2.83 (3H), 2.88 (IH), 3.09 (IH), 3.14 (2H), 3.51 (IH), 3.58 (2H), 4.04 (IH), 4.96-5.04 (2H), 5.12 (IH), 5.19 (IH), 5.28 (IH), 5.75 (IH), 5.86 (IH), 6.66 (2H), 7.35 (IH), 7.78 (IH), 7.96 (IH) ppm. Example EL8 (1 S,3S,7S, 1 OR, 11S, 12S, 16R)-[3 -(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-propyl]-carbamic acid-10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-ll-yl ester (A) and (lS,3S,7S,10R,llS,12S,16R)-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]-carbamic acid-10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[ 14.1.0]-heptadec-11 -yl ester (B) WO 2004/012735 59 PCT/EP2003/008483 29 mg (41 |amol) of the compound that is prepared according to Example EL7 is reacted analogously to Example EL2, and after purification, 18 mg (24.9 jimol, 61%) of title compound A as well as 3.0 mg (4.1 nmol, 10%) of title compound B are isolated in each case as a colorless foam. iH-NMR (CDC13) of A: 5 = 0.98 (3H), 1.05 (3H), 1.24 (3H), 1.26 (3H), 1.12-1.83 (9H), 2.12-2.46 (4H), 2.59 (2H), 2.76 (IH), 2.84 (3H), 3.14 (2H), 3.59 (3H), 3.98 (IH), 4.10 (IH), 4.95-5.02 (2H), 5.17 (2H), 5.77 (IH), 6.19 (IH), 6.70 (2H), 7.38 (IH), 7.82 (IH), 7.97 (lH)ppm. iH-NMR (CDC13) of B: 5 = 0.96 (3H), 1.01 (3H), 1.13-1.86 (11H), 1.28 (3H), 1.32 (IH), 2.16-2.50 (6H), 2.84 (3H), 3.02 (IH), 3.15 (2H), 3.50 (IH), 3.61 (2H), 3.88 (IH), 4.19 (IH), 4.96-5.04 (2H), 5.13 (IH), 5.28 (IH), 5.78 (IH), 6.33 (IH), 6.71 (2H), 7.36 (IH), 7.81 (IH), 7.96 (IH) ppm. Example EL9 (4S,7R,8S,9S,13Z,16S)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-pentyl]-carbamicacid-7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester Example EL9a (4S,7R,8S,9S,13Z,16S)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-pentyl]-carbamicacid-7-allyl-4-^r?-butyl-dimethylsilyloxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 100 mg (156 fimol) of the compound that is prepared according to Example EL7a is reacted analogously to Example ELlb with the linker that is produced according to Example L5a, and after purification, (65.9 jimol, 42%) of the title compound is isolated as a colorless oil. Example EL9 (4S,7R,8S,9S,13Z,16S)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-pentyl]-carbamicacid-7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 56 mg (65.9 |imol) of the compound that is prepared according to Example EL7b is reacted analogously to Example ELI, and after purification, 24.7 mg (33.6 [imol, 51%) of the title compound is isolated as a colorless foam. WO 2004/012735 60 PCT/EP2003/008483 iH-NMR (CDCI3): 5 = 0.97-1.84 (11H), 1.02 (3H), 1.07 (3H), 1.20 (3H), 1.71 (3H), 1.91 (IH), 2.27-2.57 (6H), 2.84 (3H), 2.88 (IH), 2.95 (IH), 3.16 (2H), 3.51 (3H), 4.02 (IH), 4.46+4.83 (IH), 4.94-5.03 (2H), 5.15 (IH), 5.20 (IH), 5.74 (IH), 5.84 (IH), 6.68 (2H), 7.35 (IH), 7.80 (IH), 7.96 (IH) ppm. Example ELI 0 (lS,3S,7S,10R,llS,12S,16R)-[5-(2,5~Dioxo-2,5-dihydro-pyrrol-l-yl)-pentyl]-carbamic acid-10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-l 1-yl ester (A) and (lS,3S,7S,10R,llS,12S,16R)-[5-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-pentyl]-carbamic acid-10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[l 4.1.0]hepta-dec-l 1 -yl ester (B) 24.7 mg (33.6 nmol) of the compound that is prepared according to Example EL9 is reacted analogously to Example EL2, and after purification, 16.7 mg (22.2 jimol, 66%) of title compound A as well as 2.0 mg (2.7 ji.mol, 8%) of title compound B are isolated in each case as a colorless foam. iH-NMR (CDCI3) of A: 8 = 0.98 (3H), 1.04 (3H), 1.10-1.75 (13H), 1.23 (3H), 1.26 (3H), 2.09-2.62 (6H), 2.75 (IH), 2.84 (3H), 3.15 (2H), 3.51 (2H), 3.57 (IH), 3.99 (IH), 4.08 (IH), 4.46+4.74 (IH), 4.93-5.02 (2H), 5.18 (IH), 5.76 (IH), 6.18 (IH), 6.68 (2H), 7.38 (IH), 7.82 (IH), 7.97 (IH) ppm. iH-NMR (CDCI3) of B: 8 = 0.83-1.85 (13H), 0.95 (3H), 1.01 (3H), 1.27 (3H), 1.32 (3H), 2.17-2.49 (6H), 2.84 (3H), 3.03 (IH), 3.17 (2H), 3.48 (IH), 3.53 (2H), 3.86 (IH), 4.18 (IH), 4.66 (IH), 4.94-5.03 (2H), 5.27 (IH), 5.76 (IH), 6.33 (IH), 6.69 (2H), 7.35 (IH), 7.81 (IH), 7.96 (IH) ppm. Example ELI 1 (lS,3S(E),7S,10R,llS,12S,16R)-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-propyl]-carbamic acid7-[3-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-propylcarbamoyloxy]-8,8,10,12,16-pentamethyl-3-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-l 1-yl ester 10 mg (19.7 nmol) of (1S,3S(E),7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[l -methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadecane is reacted analogously to Example ELlb with the linker that is produced according to Example L4a, and after purification, 7 mg (8.06 jimol, 41%) of the title compound is isolated as a colorless oil. WO 2004/012735 61 PCT/EP2003/008483 iH-NMR (CDCI3): 8 = 0.88-2.20 (13H), 1.03 (3H), 1.05 (3H), 1.10 (3H), 1.24 (3H), 1.28 (3H), 2.08 (3H), 2.63-2.85 (4H), 2.71 (3H), 2.99-3.25 (3H), 3.41-3.50 (3H), 3.62 (2H), 4.88-5.70 (5H), 6.52 (IH), 6.69 (2H), 6.71 (2H), 7.02 (IH) ppm. 5 Example EL 12 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-phenylester 10 Example EL12a (4S,7R,8S,9S,13Z,16S)-Chlorofonnicacid-7-allyl-8-(ferf-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester The solution of 1.0 g (1.56 mmol) of the compound, prepared according to 15 Example ELla, in 20 ml of dichloromethane is mixed at 0°C with the solution of 285 mg of triphosgene in 6 ml of dichloromethane, 160 jj.1 of pyridine, and it is stirred for 2.5 hours at 23°C. It is concentrated by evaporation, the residue is dissolved in ethyl acetate, washed with water and saturated sodium chloride solution, and dried over magnesium sulfate. The residue that is obtained after filtration and removal of the 20 solvent is purified by chromatography on fine silica gel. 1.08 g (1.53 mmol, 98%) of the title compound is isolated. Example EL 12b (4S ,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-8-(/er/-butyl-dimethyl-silanyloxy)-25 5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)~2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-phenyl ester The solution of267 mg (370 jamol) of the compound, prepared according to Example ELI 2a, in 16 ml of ethyl acetate, is mixed with 51 |xl of triethylamine, 700 mg of the compound that is prepared according to Example L8, and it is stirred for 16 30 hours at 23°C. It is poured into water, extracted several times with ethyl acetate, the combined organic extracts are washed with saturated sodium chloride solution and dried over magnesium sulfate. The residue that is obtained after filtration and removal WO 2004/012735 PCT/EP2003/008483 62 of the solvent is purified by chromatography on fine silica gel. 188 mg (219 |_imol, 59%) of the title compound is isolated. Example EL12 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-l 3-en-4-yl ester 4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-phenyl ester Analogously to Example ELI, 248 mg (289 junol) of the compound that is prepared according to Example EL12a is reacted, and after working-up and purification, 149 mg (201 nmol, 69%) of the title compound is isolated. *H-NMR (CDCI3): 5 = 1.08 (3H), 1.14 (3H), 1.26 (3H), 1.04-1.90 (8H), 2.24-2.57 (6H), 2.68-2.99 (3H), 2.81 (3H), 3.45 (IH), 3.72 (IH), 5.02 (IH), 5.06 (IH), 5.17 (IH), 5.65 (IH), 5.74 (IH), 5.98 (IH), 6.79 (2H), 6.88 (2H), 7.21 (2H), 7.33 (IH), 7.64 (IH), 7.97 (IH) ppm. Example ELI 3 (1S,3S,7S,10R,1 lS,12S,16R)-Carbonic acid-10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-phenyl ester Analogously to Example EL2,144 mg (194 |amol) of the compound that is prepared according to Example EL12 is reacted, and after working-up and purification, 89 mg (117 nmol, 60%) of the title compound is isolated. lH-NMR(CDCl3): 5 = 1.10 (3H), 1.14 (3H), 1.27 (3H), 1.32 (3H), 1.19-1.85 (7H), 2.08-2.89 (8H), 2.81 (3H), 3.50 (IH), 3.70 (IH), 5.02 (IH), 5.07 (IH), 5.58 (IH), 5.72 (IH), 6.10 (IH), 6.81 (2H), 6.88 (2H), 7.21 (2H), 7.31 (IH), 7.68 (IH), 7.93 (IH) ppm. Example EL14 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-l 3-en-8-yl ester 4-(2,5-dioxo-2,5-dihydro-pyrrol-1 -yl)-phenyl ester Example EL 14a WO 2004/012735 PCT/EP2003/008483 63 (4S,7R,8S,9S, 13Z, 16S)-Chloroformic acid-7-allyl-4-(rert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-8-yl ester Analogously to Example EL12a, 1.0 g (1.56 mmol) of the compound that is prepared according to Example EL7a is reacted, and 1.05 g (1.49 mmol, 96%) of the title compound is isolated. Example EL14b (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-4-(/er/-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-phenyl ester The solution of 313 mg (0.44 mmol) of the compound, prepared according to Example ELI 4a, in 19 ml of ethyl acetate is mixed with 840 mg of the compound that is prepared according to Example L8,61.5 jxl of triethylamine, and it is stirred for 16 hours at 23°C. It is mixed with water, extracted several times with ethyl acetate, the combined organic extracts are washed with saturated sodium chloride solution and dried over sodium sulfate. The residue that is obtained after filtration and removal of the solvent is purified by chromatography on fine silica gel. 298 mg (348 fxmol, 79%) of the title compound is isolated. Example EL 14 (4S ,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-phenyl ester Analogously to Example ELI, 304 mg (355 jimol) of the compound that is prepared according to Example EL14a is reacted, and after working-up and purification, 67 mg (90 |imol, 25%) of the title compound is isolated. *H-NMR (CDC13): 8= 1.09 (3H), 1.11 (3H), 0.84-2.02 (7H), 1.27 (3H), 1.72 (3H), 2.29-2.58 (6H), 2.84 (3H), 2.89 (IH), 2.96 (IH), 3.63 (IH), 4.03 (IH), 5.06 (2H), 5.23 (2H), 5.80 (IH), 5.85 (IH), 6.86 (2H), 7.30 (2H), 7.35 (IH), 7.39 (IH), 7.80 (IH), 7.96 (IH) ppm. Example ELI 5 WO 2004/012735 PCT/EP2003/008483 64 (1 S,3S,7S, 10R, 11 S,12S, 16R)-Carbonic acid-10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yl ester 4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-phenyl ester Analogously to Example EL2,67 mg (90 |imol) of the compound that is prepared according to Example ELM is reacted, and after working-up and purification, 32 mg (42 nmol, 47%) of the title compound is isolated. iH-NMR (CDC13): 8 = 1.05 (3H), 1.06 (3H), 1.25 (3H), 1.35 (3H), 1.21-1.90 (7H), 2.18 (2H), 2.33-2.67 (4H), 2.73 (IH), 2.85 (3H), 3.79 (IH), 4.11 (IH), 4.33 (IH), 5.02 (IH), 5.07 (IH), 5.31 (1H), 5.81 (IH), 6.27 (IH), 6.86 (2H), 7.29 (2H), 7.35-7.41 (3H), 7.83 (IH), 7.99 (IH) ppm. Example ELI 6 (lS,3S(E),7S,10R,llS,12S,16R)-JV-[l-({4-[2-(7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-3-yl)-propenyl]-thiazol-2-ylmethyl} -carbamoyl)-ethyl]-3 -methyltrisulfanyl-iV-methyl-propionamide The solution of 7 mg (13 ^imol) of (lS,3S(E),7S,10R,llS,12S,16R)-3-[2-(2-aminomethyl-thiazol-4-yl)-1 -methyl-vinyl]-7,11 -dihydroxy-8,8,10,12,16-penta-methyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione, which was produced analogously to the process described in WO 99/01124, in 0.5 ml of dichloromethane is mixed with 7 mg of the compound that is prepared according to Example LI, 0.4 mg of 4-dimethylaminopyridine and 4 mg of N,N'-dicyclohexylcarbodiimide are added, and it is stirred for 20 minutes at 23°C. Precipitated urea is filtered out, and it is purified by chromatography on a preparative thin-layer plate. 5 mg (6.5 nmol, 50%) of the title compound is isolated. iH-NMR (CDCI3): 8 = 1.00 (3H), 1.08 (3H), 1.17 (3H), 1.23-1.77 (5H), 1.28 (3H), 1.36 (3H), 1.39 (3H), 1.88-2.13 (3H), 2.10 (3H), 2.37 (IH), 2.49-2.66 (2H), 2.55 (3H), 2.77-2.92 (4H), 2.97 (3H), 3.16 (2H), 3.31 (IH), 3.77 (IH), 4.08 (IH), 4.19 (IH), 4.62 (IH), 4.76 (IH), 5.25 (IH), 5.45 (IH), 6.57 (IH), 7.01 (IH), 7.06 (IH) ppm. Example ELI 7 (lS,3S(E),7S,10R,llS,12S,16R)-2-[Methyl-(3-methyltrisulfanyl-propionyl)-amino]-propionic acid-4-[2-(7,11 -dihydroxy-8,8,10,12,16-pentamethyl-5,9-dioxo-4,17-dioxa-bicyclo[l 4.1.0]heptadec-3-yl)-propenylJ-thiazol-2-ylmethyl ester WO 2004/012735 PCT/EP2003/008483 65 Analogously to Example EL16,10 mg (19 nmol) of (1S,3S(E),7S,10R,11S, 12S, 16R)-7,11 -dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-l-methyl-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo [ 14.1.0] heptadecane-5,9-dione, which was produced analogously to the process that is described in WO 99/01124, is reacted, and 2.2 mg (2.8 |_imol, 15%) of the title compound is isolated. iH-NMR (CDC13): 5=1.01 (3H), 1.09 (3H), 1.18 (3H), 1.27 (IH), 1.28 (3H), 1.32-1.76 (3H), 1.37 (3H), 1.47 (3H), 1.95 (IH), 2.06 (IH), 2.12 (3H), 2.38 (IH), 2.51-2.63 (2H), 2.56 (3H), 2.78-2.92 (5H), 2.97+3.01 (3H), 3.13-3.35 (3H), 3.71 (IH), 3.77 (IH), 4.00 (IH), 4.18 (IH), 5.25 (IH), 5.39 (2H), 5.45 (IH), 6.60 (IH), 7.17 (IH) ppm. Example ELI 8 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l -yl)-butanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7-aIlyl-8-hydroxy-5,5,9,13-tetramethyI-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Example ELI 8a 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l -yl)-butanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7-allyl-8-(fer?-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example EL12b, 200 mg (284 nmol) of the compound that is prepared according to Example EL12a is reacted with 770 mg of the compound that is prepared according to Example L9, and after working-up and purification, 129 mg (129 nmol, 45%) of the title compound is isolated. Example ELI 8 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELI, 129 mg (129 fimol) of the compound that is prepared according to Example EL 18a is reacted, and after working-up and purification, 71 mg (80 nmol, 62%) of the title compound is isolated. WO 2004/012735 PCT/EP2003/008483 66 iH-NMR (CDCI3): 8 = 0.88-2.11 (1 IH), 1.02 (3H), 1.14 (3H), 1.71 (3H), 2.23-2.56 (6H), 2.63-2.71 (3H), 2.74 (3H), 2.97 (IH), 3.39 (IH), 3.68 (3H), 4.58 (IH), 4.78 (IH), 5.01 (IH), 5.05 (IH), 5.18 (IH), 5.56 (IH), 5.71 (IH), 5.97 (IH), 6.73 (2H), 7.19 (IH), 7.31 (IH), 7.36 (IH), 7.75 (IH), 7.77 (IH), 7.95 (IH) ppm. Example ELI 9 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4~(1S,3S,7S,10R,11S,12S,16R)-[10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenylester (A) and 4-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-butanoic acid 4-(1R,3S,7S,1 OR, 11S, 12S, 16S)-[10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenyl ester (B) Analogously to Example EL2,71 mg (80 jimol) of the compound that is prepared according to Example EL 18 is reacted, and after working-up and purification, 41 mg (45 |umol, 57%) of title compound A as well as 12 mg (13 jimol, 17%) of title compound B are isolated. iH-NMR (CDCI3) of A: 8 = 1.04 (3H), 1.14 (3H), 1.16 (3H), 1.32 (3H), 1.34-1.84 (6H), 2.01-2.74 (12H), 2.78 (3H), 2.86 (IH), 3.44 (IH), 3.68 (3H), 4.56 (IH), 4.74 (IH), 5.01 (IH), 5.06 (IH), 5.47 (IH), 5.70 (IH), 6.07 (IH), 6.73 (2H), 7.20 (IH), 7.32 (IH), 7.36 (IH), 7.77 (IH), 7.81 (IH), 7.90 (IH) ppm. Example EL20 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid4-(4S}7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Example EL20a 6-(2,5-Dioxo-2,5-dihydro-pyrroI-l-yl)-hexanoic acid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-(ferf-butyl-dimethyl-silanyIoxy)-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester WO 2004/012735 67 PCT/EP2003/008483 Analogously to Example EL12b, 243 mg (345 jimol) of the compound that is prepared according to Example EL12a is reacted with 1 g of the compound that is prepared according to Example L10, and after working-up and purification, 25 mg (24 ^mol, 7%) of the title compound is isolated. Example EL20 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyI-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELI, 212 mg (206 (xmol) of the compound that is prepared according to Example EL20a is reacted, and after working-up and purification, 117 mg (128 jimol, 62%) of the title compound is isolated. iH-NMR (CDCI3): 5 = 1.01 (3H), 1.14 (6H), 1.04-2.78 (20H), 1.70 (3H), 2.74 (3H), 2.97 (IH), 3.39 (IH), 3.56 (2H), 3.68 (IH), 4.11 (IH), 4.58 (IH), 4.77 (IH), 5.00 (IH), 5.05 (IH), 5.18 (IH), 5.56 (IH), 5.71 (IH), 5.97 (IH), 6.69 (2H), 7.12 (IH), 7.29 (IH), 7.36 (IH), 7.75 (2H), 7.94 (IH) ppm. Example EL21 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(lS,3S,7S,10R,l 1S,12S,16R)-[10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[l 4.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenyl ester (A) and 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(1R,3S,7S,10R,11S,12S,16S)-[10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenyl ester (B) Analogously to Example EL2,117 mg (128 jimol) of the compound that is prepared according to Example EL20 is reacted, and after working-up and purification, 63 mg (68 jimol, 53%) of title compound A as well as 19 mg (20 jimol, 16%) of title compound B are isolated. iH-NMR (CDCI3) of A: 6 = 1.03 (3H), 1.14 (3H), 1.15 (3H), 1.32 (3H), 1.07-2.75 (22H), 2.77 (3H), 2.86 (IH), 3.44 (IH), 3.55 (2H), 3.69 (IH), 4.55 (IH), 4.77 (IH), 5.01 (IH), 5.06 (IH), 5.47 (IH), 5.70 (IH), 6.08 (IH), 6.70 (2H), 7.14 (IH), 7.31 (IH), 7.35 (IH), 7.76 (IH), 7.80 (IH), 7.90 (IH) ppm. WO 2004/012735 PCT/EP2003/008483 68 Example EL22 1 l-(2,5-Dioxo-2,5-dihydro-pyrroM-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Example EL22a 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-(terNbutyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example EL12b, 243 mg (345 |jjmol) of the compound that is prepared according to Example EL12a is reacted with 1.19 g of the compound that is prepared according to Example LI 1, and after working-up and purification, 171 mg (155 nmol, 45%) of the title compound is isolated. Example EL22 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELI, 171 mg (155 |j,mol) of the compound that is prepared according to Example EL22a is reacted, and after working-up and purification, 108 mg (110 pmol, 71%) of the title compound is isolated. iH-NMR (CDC13): 6 = 1.02 (3H), 1.14 (6H), 0.88-2.56 (28H), 1.70 (3H), 2.63 (2H), 2.71 (IH), 2.74 (3H), 2.98 (IH), 3.39 (IH), 3.50 (2H), 3.69 (IH), 4.58 (IH), 4.77 (IH), 5.00 (IH), 5.05 (IH), 5.17 (IH), 5.56 (IH), 5.71 (IH), 5.97 (IH), 6.68 (2H), 7.11 (IH), 7.29 (IH), 7.36 (IH), 7.75 (IH), 7.76 (IH), 7.94 (IH) ppm. Example EL23 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(1 S,3 S,7 S, 1 OR, 11S, 12S,16R)-[ 10-allyl-l 1 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenyl ester (A) and ll-(2,5-Dioxo-2,5-dihydro- WO 2004/012735 PCT/EP2003/008483 69 pyrrol-l-yl)-undecanoic acid 4-(lR,3S,7S,10R,l 1S,12S, 16S)-[10-allyl-l 1-hydroxy-8,8)12J16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenyl ester (B) Analogously to Example EL2,108 mg (110 jimol) of the compound that is prepared according to Example EL22 is reacted, and after working-up and purification, 65.9 mg (65.8 jumol, 60%) of title compound A as well as 19.8 mg (20 jamol, 18%) of title compound B are isolated. iH-NMR (CDC13) of A: 8 = 1.04 (3H), 1.14 (3H), 1.15 (3H), 1.63 (3H), 0.92-1.85 (23H), 2.10-2.81 (9H), 2.77 (3H), 2.86 (IH), 3.45 (IH), 3.51 (2H), 3.69 (IH), 4.55 (IH), 4.74 (IH), 5.01 (IH), 5.06 (IH), 5.47 (IH), 5.70 (IH), 6.08 (IH), 6.68 (2H), 7.13 (IH), 7.31 (IH), 7.35 (IH), 7.77 (IH), 7.80 (IH), 7.90 (IH) ppm. Example EL24 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Example EL24a 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-(fer^-butyl-dimethyl-silanyloxy)-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example EL12b, 271 mg (385 |imol) of the compound that is prepared according to Example EL14a is reacted with 1.04 g of the compound that is prepared according to Example L9, and after working-up and purification, 193 mg (193 (amol, 50%) of the title compound is isolated. Example EL24 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-nitro-phenyl ester WO 2004/012735 PCT/EP2003/008483 70 Analogously to Example ELI, 193 mg (193 |imol) of the compound that is prepared according to Example EL24a is reacted, and after working-up and purification, 107 mg (120 |imol, 62%) of the title compound is isolated. iH-NMR (CDC13): 8=1.02 (3H), 1.07 (3H), 1.23 (3H), 0.97-2.13 (8H), 1.71 (3H), 2.28-2.54 (6H), 2.67 (2H), 2.84 (3H), 2.88 (IH), 2.95 (IH), 3.56 (IH), 3.67 (2H), 4.01 (IH), 4.93 (IH), 4.98 (IH), 5.17 (IH), 5.22 (3H), 5.70 (IH), 5.84 (IH), 6.72 (2H), 7.30 (IH), 7.34 (IH), 7.69 (IH), 7.80 (IH), 7.95 (IH), 8.13 (IH) ppm. Example EL25 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(lS,3S,7S,10R,l 1S,12S,16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1.0]heptadec-11 -yloxycarbonyloxymethyl]-2-nitro-phenyl ester (A) and 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(1R,3S,7S,10R,11S,12S,16S)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1.0]heptadec-l 1 -yloxycarbonyloxymethyl]-2-nitro-phenyl ester (B) Analogously to Example EL2,102 mg (115 p.mol) of the compound that is prepared according to Example ELI 9 is reacted, and after working-up and purification, 65 mg (72 jimol, 63%) of title compound A as well as 3 mg (3.3 jimol, 3%) of title compound B are isolated. iH-NMR (CDCI3) of A: 8 = 0.97 (3H), 1.04 (3H), 1.23 (3H), 1.31 (3H), 1.10-2.75 (18H), 2.85 (3H), 3.68 (2H), 3.71 (IH), 4.09 (IH), 4.28 (IH), 4.92 (IH), 4.97 (IH), 5.20 (2H), 5.23 (IH), 5.72 (IH), 6.26 (IH), 6.72 (2H), 7.30 (IH), 7.37 (IH), 7.68 (IH), 7.83 (IH), 7.98 (IH), 8.13 (IH) ppm. Example EL26 6-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-hexanoic acid 4-(4S,7R, 8S,9S, 13Z, 16S)-[7-allyl-4-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Example EL26a 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7- allyl-4-(fe/Y-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl- WO 2004/012735 PCT/EP2003/008483 71 benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-8-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example EL12b, 273 mg (387 jxmol) of the compound that is prepared according to Example EL 14a is reacted with 1.12 g of the compound that is prepared according to Example L10, and after working-up and purification, 69 mg (67 jimol, 17%) of the title compound is isolated. Example EL26 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELI, 69 mg (67 jimol) of the compound that is prepared according to Example EL26a is reacted, and after working-up and purification, 26 mg (28 jimol, 42%) of the title compound is isolated. iH-NMR (CDC13): 5 = 0.93 (3H), 0.95 (3H), 1.16 (3H), 1.60 (3H), 0.98-2.61 (20H), 2.73 (3H), 2.77 (IH), 3.45 (3H), 3.83 (IH), 4.05 (IH), 4.83 (IH), 4.88 (IH), 5.05 (IH), 5.13 (3H), 5.62 (IH), 5.74 (IH), 6.61 (2H), 7.16 (IH), 7.26 (IH), 7.60 (IH), 7.70 (IH), 7.88 (IH), 8.03 (IH) ppm. Example EL27 6-(2,5-Dioxo~2,5-dihydro-pyrrol-1 -yl)-hexanoic acid 4-( 1 S,3 S,7S, 1 OR, 11 S,12S, 16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-nitro-phenyl ester (A) and 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l -yI)-hexanoic acid 4-(1 R,3S,7S, 1 OR, 11S, 12S, 16S)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo [14.1 .OJheptadec-11-yloxycarbonyloxymethyl]-2-nitro-phenyl ester (B) Analogously to Example EL2,38 mg (41 jimol) of the compound that is prepared according to Example ELI 9 is reacted, and after working-up and purification, 14 mg (15 jimol, 37%) of title compound A as well as 2 mg (2 jimol, 5%) of title compound B are isolated. iH-NMR (CDCI3) of A: 8 = 0.96 (3H), 1.03 (3H), 1.08-1.86 (13H), 1.23 (3H), 1.30 (3H), 2.16 (2H), 2.23-2.78 (7H), 2.83 (3H), 3.54 (2H), 3.71 (IH), 4.09 (IH), 4.27 WO 2004/012735 PCT/EP2003/008483 72 (IH), 4.91 (IH), 4.96 (IH), 5.21 (3H), 5.72 (IH), 6.25 (IH), 6.69 (2H), 7.23 (IH), 7.36 (IH), 7.67 (IH), 7.82 (IH), 7.96 (IH), 8.11 (IH) ppm. Example EL28 ll-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5 -yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Example EL28a 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S313Z,16S)-[7-allyl-4-(ter/-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyIoxymethyl]-2-nitro-phenyl ester Analogously to Example EL12b, 273 mg (387 junol) of the compound that is prepared according to Example EL14a is reacted with 1.34 g of the compound that is prepared according to Example Lll, and after working-up and purification, 196 mg (178 nmol, 46%) of the title compound is isolated. Example EL28 I l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELI, 196 mg (178 jimol) of the compound that is prepared according to Example EL28a is reacted, and after working-up and purification, 100 mg (101 jimol, 57%) of the title compound is isolated. iH-NMR (CDCI3): 6 = 1.03 (3H), 1.06 (3H), 1.23 (3H), 1.70 (3H), 0.99-1.81 (21H), 1.91 (IH), 2.27-2.53 (6H), 2.63 (2H), 2.83 (3H), 2.88 (IH), 2.95 (IH), 3.51 (2H), 3.56 (IH), 4.00 (IH), 4.92 (IH), 4.98 (IH), 5.13-5.26 (4H), 5.71 (IH), 5.83 (IH), 6.68 (2H), 7.23 (IH), 7.34 (IE), 7.67 (IH), 7.79 (IE), 7.95 (IH), 8.13 (IH) ppm. Example EL29 II -(2,5-Dioxo-2,5-dihydro-pyrroI-1 -yl)-undecanoic acid 4- (1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-[10-allyl-7-hydroxy-8,8,l 2,16-tetramethyl-3-(2-methyl- WO 2004/012735 PCT/EP2003/008483 73 benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1 .OJheptadec-1 1 -yloxycarbonyloxymethyl]-2-nitro-phenyl ester (A) and ll-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(lR,3S,7S,10R,l IS, 12S,16S)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-nitro-phenyl ester (B) Analogously to Example EL2,100 mg (101 jimol) of the compound that is prepared according to Example EL 19 is reacted, and after working-up and purification, 21 mg (21 jimol, 21%) of title compound A as well as 2 mg (2 jimol, 2%) of title compound B are isolated. iH-NMR (CDCI3) of A: 5 = 0.97 (3H), 1.04 (3H), 1.23 (3H), 0.84-1.84 (24H), 1.71 (3H), 2.15 (2H), 2.23-2.68 (5H), 2.71 (IH), 2.83 (3H), 3.50 (2H), 3.71 (IH), 4.09 (IH), 4.27 (IH), 4.91 (IH), 4.96 (IH), 5.19 (2H), 5.23 (IH), 5.72 (IH), 6.26 (IH), 6.68 (2H), 7.23 (IH), 7.36 (IH), 7.66 (IH), 7.83 (IH), 7.97 (IH), 8.12 (IH) ppm. Example EL30 4-(2,5-Dioxo-2,5-dihydro-pyrrol- l-yl)-butanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-phenyl ester Example EL30a 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-4-yloxycarbonyloxymethyI]-phenyl ester Analogously to Example EL12b, 218 mg (309 jimol) of the compound prepared according to Example EL12a are reacted with 314 mg of the compound prepared according to Example L12. After working-up and purification, 103 mg (118 jimol, 35%) of the title compound are isolated. Example EL30 WO 2004/012735 74 PCT/EP2003/008483 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid 4-(4S,7R,8S,9S,13Z,16S)-[7- allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo- oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example ELI, 103 mg (118 jamol) of the compound prepared according to Example EL30a are reacted. After working-up and purification, 13 mg (15 junol, 13%) of the title compound are isolated. !H-NMR (CDCI3): 8= 0.88-1.84 (7H), 1.00 (3H), 1.12 (3H), 1.14 (3H), 1.71 (3H), 2.04 (2H), 2.23-2.71 (8H), 2.74 (3H), 2.99 (IH), 3.40 (IH), 3.67 (3H), 4.48 (IH), 4.76 (IH), 5.00 (IH), 5.04 (IH), 5.18 (IH), 5.55 (IH), 5.71 (IH), 5.98 (IH), 6.72 (2H), 7.01 (2H), 7.08 (2H), 7.37 (IH), 7.76 (IH), 7.96 (IH) ppm. Example EL31 4-(255-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(lS,3S,7S,10R,llS,12S, 16R)-[ 10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyI-benzothiazol-5-yi)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyI]-phenyl ester Analogously to Example EL2,13 mg (15 jimol) of the compound prepared according to Example EL30 are reacted. After working-up and purification, 5.7 mg (6.6 jimol, 44%) of the title compound are isolated. ^-NMR (CDCI3) of A: 8 = 1.04 (3H), 1.14 (3H), 1.16 (3H), 1.32 (3H), 1.34-1.84 (6H), 2.04 (2H), 2.15-2.75 (10H), 2.78 (3H), 2.85 (IH), 3.44 (IH), 3.67 (3H), 4.48 (IH), 4.73 (IH), 5.01 (IH), 5.05 (IH), 5.47 (IH), 5.70 (IH), 6.07 (IH), 6.72 (2H), 7.02 (2H), 7.13 (2H), 7.31 (IH), 7.77 (IH), 7.93 (IH) ppm. Example EL32 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5s5,9513-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxyme1hyl]-phenyl ester Example EL32a 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyciohexadec-13-en-4-yloxycarbonyloxymethyl]-phenyl ester WO 2004/012735 75 PCT/EP2003/008483 Analogously to Example EL12b, 218 mg (309 fimol) of the compound prepared according to Example EL12a are reacted with 396 mg of the compound prepared according to Example L13. After working-up and purification, 157 mg (159 |imol, 51%) of the title compound are isolated. Example EL32 6-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-hexanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7- allyl-8-hydroxy-5,5,9,13-tetramethyl-16~(2-methyl-benzothiazol-5-yl)-2,6-dioxo- oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example ELI, 157 mg (159 |j.mol) of the compound prepared according to Example EL32a are reacted. After working-up and purification, 32 mg (37 jimol, 23%) of the title compound are isolated. ^-NMR (CDCI3): 8 = 0.99 (3H), 1.12 (3H), 1.14 (3H), 1.04-2.84 (20H), 1.70 (3H), 2.75 (3H), 3.00 (IH), 3.40 (IH), 3.55 (2H), 3.68 (IH), 4.48 (IH), 4.76 (IH), 5.00 (IH), 5.04 (IH), 5.18 (IH), 5.55 (IH), 5.71 (IH), 5.98 (IH), 6.69 (2H), 6.98 (2H), 7.07 (2H), 7.37 (IH), 7.76 (2H), 7.96 (IH) ppm. Example EL33 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(lS,3S,7S,10R,llS,12S, 16R)-[10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example EL2, 30 mg (34 jimol) of the compound prepared according to Example EL32 are reacted. After working-up and purification, 13 mg (15 [imol, 44%) of the title compound are isolated. !H-NMR (CDCI3) of A: 8 = 1.01 (3H), 1.13 (3H), 1.14 (3H), 1.32 (3H), 1.07-2.75 (22H), 2.78 (3H), 2.85 (IH), 3.44 (IH), 3.55 (2H), 3.69 (IH), 4.48 (IH), 4.73 (IH), 5.01 (IH), 5.05 (IH), 5.45 (IH), 5.70 (IH), 6.08 (IH), 6.69 (2H), 6.99 (2H), 7.12 (2H), 7.32 (IH), 7.77 (IH), 7.92 (IH) ppm. Example EL34 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16~(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-4-yloxycarbonyloxymethyl] -phenyl ester WO 2004/012735 PCT/EP2003/008483 76 Example EL34a 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,l3Z, 16S)-[7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example EL12b, 218 mg (309 jimol) of the compound prepared according to Example EL12a are reacted with 422 mg of the compound prepared according to Example LI4. After working-up and purification, 77 mg (73 jimol, 24%) of the title compound are isolated. Example EL34 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7- allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo- oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example ELI, 77 mg (73 jimol) of the compound prepared according to Example EL34a are reacted. After working-up and purification, 14 mg (15 jimol, 20%) of the title compound are isolated. 'H-NMR (CDCfe): 8 = 0.99 (3H), 1.11 (3H), 1.14 (3H), 0.88-1.88 (22H), 1.70 (3H), 2.24-2.58 (8H), 2.67 (IH), 2.75 (3H), 3.00 (IH), 3.40 (IH), 3.51 (2H), 3.68 (IH), 4.48 (IH), 4.76 (IH), 5.00 (IH), 5.04 (IH), 5.18 (IH), 5.55 (IH), 5.71 (IH), 5.98 (IH), 6.68 (2H), 6.98 (2H), 7.07 (2H), 7.37 (IH), 7.76 (IH), 7.96 (IH) ppm. Example EL35 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(lS,3S,7S,10R,l 1S,12S, 16R)-[10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example EL2, 14 mg (15 jimol) of the compound prepared according to Example EL34 are reacted. After working-up and purification, 6 mg (6 jimol, 42%) of the title compound are isolated. 'H-NMR (CDC13) von A: 8 = 1.01 (3H), 1.14 (6H), 1.20-1.90 (26H), 2.12-2.58 (8H), 2.71 (IH), 2.77 (3H), 2.85 (IH), 3.44 (IH), 3.51 (2H), 3.69 (IH), 4.48 (IH), 4.73 (IH), WO 2004/012735 PCT/EP2003/008483 77 5.01 (IH), 5.05 (IH), 5.45 (IH), 5.70 (IH), 6.08 (IH), 6.68 (2H), 6.99 (2H), 7.12 (2H), 7.31 (IH), 7.77 (IH), 7.92 (IH) ppm. Example EL36 4-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-butanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-phenyl ester Example EL36a 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example EL12b, 330 mg (470 nmol) of the compound prepared according to Example EL 14a are reacted with 544 mg of the compound prepared according to Example L12. After working-up and purification, 170 mg (178 nmol, 38%) of the title compound are isolated. Example EL36 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-8-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example ELI, 170 mg (178 jimol) of the compound prepared according to Example EL36a are reacted. After working-up and purification, 21 mg (24 jimol, 14%) of the title compound are isolated. 'H-NMR (CDCI3): 8 = 1.02 (3H), 1.07 (3H), 1.22 (3H), 0.97-2.13 (8H), 1.70 (3H), 2.28-2.63 (8H), 2.84 (3H), 2.82-2.95 (2H), 3.55 (IH), 3.67 (2H), 3.97 (IH), 4.92 (IH), 4.96 (IH), 5.15 (IH), 5.16 (2H), 5.22 (IH), 5.70 (IH), 5.82 (IH), 6.68 (2H), 7.08 (2H), 7.34 (IH), 7.41 (2H), 7.79 (IH), 7.94 (IH) ppm. Example EL37 4-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-butanoic acid 4-(lS,3S,7S,10R,l 1S,12S, 16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo- WO 2004/012735 PCT/EP2003/008483 78 4,17-dioxa-bicyclo[ 14.1.0]heptadec-11 -yloxycarbonyloxymethylJ-2-nitro-phenyl ester (A) and 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-( 1 R,3 S,7S, 1 OR, 11S, 12S, 16S)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-5 4,17-dioxa-bicyclo[14.1.0]heptadec-l l-yloxycarbonyloxymethyl]-phenyl ester (B) 32 mg (38|amol) of the compound prepared according to Example EL36 are reacted. After working-up and purification, 10.1 mg ( 12 jumol, 31%) of title compound A as well as 1.2 mg (1.4 (imol, 3,7%) of title compound B are isolated. 'H-NMR (CDCls) of A: 8 = 0.96 (3H), 1.04 (3H), 1.24 (3H), 1.29 (3H), 0.90-1.78 10 (7H), 2.04 (2H), 2.16 (2H), 2.20-2.62 (6H), 2.72 (IH), 2.84 (3H), 3.67 (2H), 3.69 (IH), 4.07 (IH), 4.20 (IH), 4.91 (IH), 4.95 (IH), 5.14 (2H), 5.22 (IH), 5.72 (IH), 6.24 (IH), 6.71 (2H), 7.10 (2H), 7.37 (IH), 7.40 (2H), 7.88 (IH), 7.97 (IH) ppm. Example EL38 15 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5 -y!)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-phenyl ester Example EL38a 20 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example EL12b, 450 mg (640 jimol) of the compound prepared 25 according to Example EL 14a are reacted with 811 mg of the compound prepared according to Example L13. After working-up and purification, 108 mg (110 jimol, 17%) of the title compound are isolated. Example EL38 30 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-phenyl ester WO 2004/012735 PCT/EP2003/008483 79 108mg (110 |imol) of the compound prepared according to Example EL38a in 22 ml dichloromethane are mixed with 1.06 ml (2.74 mmol) of a 20% solution of trifluoroacetic acid in dichloromethane. After 16 hours the mixture is diluted with dichloromethane and poured into a saturated solution of sodium bicarbonate. The 5 mixture is extracted several times with dichloromethane and the combined organic extracts are dried over sodium sulfate. The residue obtained by filtration and removal of the solvent is purified by chromatography on fine silica gel. 64 mg (73 nmmol, 67%) of the title compound are isolated. 'H-NMR (CDC13): 5 = 1.02 (3H), 1.07 (3H), 1.16 (3H), 1.70 (3H), 0.98-1.96 (12H), 10 2.25-2.58 (8H), 2.83 (3H), 2.90 (2H), 3.55 (3H), 3.97 (IH), 4.92 (IH), 4.96 (IH), 5.15 (IH), 5.16 (2H), 5.22 (IH), 5.70 (IH), 5.82 (IH), 6.69 (2H), 7.08 (2H), 7.34 (IH), 7.41 (2H), 7.79 (IH), 7.94 (IH) ppm. Example EL39 15 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4~(1S,3S,7S,10R,1 1S,12S, 16R)-[ 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-l l-yloxycarbonyloxymethyl]-phenyl ester (A) und 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(lR,3 S,7S,10R,11S, 12S, 16S)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-20 4,17-dioxa-bicyclo[14.1.0]heptadec-l l-yloxycarbonyloxymethyl]-phenyl ester (B) Analogously to Example EL2, 64 mg (73 jimol) of the compound prepared according to Example EL38 are reacted. After working-up and purification, 25 mg (28 nmol, 39%) of the title compound A as well as 5.4 mg (6.1 jimol, 8.3%) of the title compound B are isolated. 25 'H-NMR (CDCI3) of A: 5 = 0.96 (3H), 1.04 (3H), 1.13-1.82 (13H), 1.23 (3H), 1.29 (3H), 2.15 (2H), 2.22-2.64 (6H), 2.71 (IH), 2.84 (3H), 3.54 (2H), 3.69 (IH), 4.08 (IH), 4.20 (IH), 4.91 (IH), 4.95 (IH), 5.14 (2H), 5.22 (IH), 5.72 (IH), 6.24 (IH), 6.69 (2H), 7.07 (2H), 7.37 (IH), 7.40 (2H), 7.82 (IH), 7.97 (IH) ppm. 30 Example EL40 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-phenyl ester WO 2004/012735 80 PCT/EP2003/008483 Example EL40a 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13 -tetramethyl-16-(2-methyl- benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example EL 12b, 450 mg (640 |imol) of the compound prepared according to Example EL14a are reacted with 992 mg of the compound prepared according to Example L14. After working-up and purification, 67 mg (63 nmol, 10%) of the title compound are isolated. Example EL40 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7- allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo- oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example EL38,67 mg (63 [imol) of the compound prepared according to Example EL40a are reacted. After working-up and purification, 23 mg (24 |imol, 38%) of the title compound are isolated. 'H-NMR (CDC13): 8 = 1.02 (3H), 1.07 (3H), 1.21 (3H), 1.70 (3H), 0.99-1.81 (21H), 1.91 (IH), 2.27-2.58 (8H), 2.83 (3H), 2.89 (2H), 3.50 (2H), 3.55 (IH), 3.97 (IH), 4.92 (IH), 4.96 (IH), 5.15 (IH), 5.16 (2H), 5.20 (IH), 5.70 (IH), 5.82 (IH), 6.68 (2H), 7.08 (2H), 7.34 (IH), 7.41 (2H), 7.79 (IH), 7.94 (IH) ppm. Example EL41 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(lS,3S,7S,10R,l 1S,12S, 16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo [14.1.0]heptadec-11 -yloxycarbonyloxymethyl]-phenyl ester (A) and 11 -(2,5 -Dioxo-2,5-dihydro-pyrrol-1 -yl)-undecanoic acid 4-(lR,3S,7S,10R,llS,12S,16S)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benz»thiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-l 1-yloxycarbonyloxymethylj-phenyl ester (B) Analogously to Example EL2, 33 mg (35 p.mol) of the compound prepared according to Example EL40 are reacted. After working-up and purification, 13 mg (14 jimol, WO 2004/012735 PCT/EP2003/008483 81 38%) of the title compound A as well as 4 mg (4 jimol, 12%) of the title compound B are isolated. 'H-NMR (CDCI3) of A: 8 = 0.96 (3H), 1.04 (3H), 1.23 (3H), 0.91-1.78 (27H), 2.16 (2H), 2.23-2.68 (5H), 2.71 (IH), 2.84 (3H), 3.50 (2H), 3.69 (IH), 4.07 (IH), 4.20 (IH), 4.91 (IH), 4.95 (IH), 5.14 (2H), 5.22 (IH), 5.72 (IH), 6.24 (IH), 6.68 (2H), 7.07 (2H), 7.37 (IH), 7.40 (2H), 7.82 (IH), 7.97 (IH) ppm. Example EL42 4-(2,5-Dioxo-2,5-dihydro-pyrrol- l-yl)-butanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chlor-phenyl ester Example EL42a 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(4S,7R,8S,9S,l 3Z,16S)-[7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chlor-phenyl ester Analogously to Example EL 12b, 329 mg (467|imol) of the compound prepared according to Example EL12a are reacted with 885 mg of the compound prepared according to Example L15. After working-up and purification, 126 mg (127 jimol, 27%) of the title compound are isolated. Example EL42 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chlor-phenyl ester Analogously to Example ELI, 126 mg (127 jimol) of the compound prepared according to Example EL42a are reacted. After working-up and purification, 79 mg (90 jimol, 71%) of the title compound are isolated. lH-NMR (CDCI3): 8 = 1.01 (3H), 1.13 (3H), 1.14 (3H), 1.70 (3H), 1.31-1.72 (17H), 2.75 (3H), 2.99 (IH), 3.40 (IH), 3.68 (3H), 4.49 (IH), 4.70 (IH), 5.00 (IH), 5.05 (IH), 5.18 (IH), 5.55 (IH), 5.71 (IH), 5.98 (IH), 6.72 (2H), 6.99 (IH), 7.07 (IH), 7.10 (IH), 7.36 (IH), 7.75 (IH), 7.95 (IH) ppm. WO 2004/012735 82 PCT/EP2003/008483 Example EL43 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(lS,3S,7S,10R,l 1S,12S, 16R)-[10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[l 4.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-chlor-phenyl ester (A) and 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(1R,3S,7S,10R,11S,12S, 16S)-[10-allyl-l 1 -hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[l 4.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-chlor-phenyl ester (B) Analogously to Example EL2, 66 mg (75 |xmol) of the compound prepared according to Example EL42 are reacted. After working-up and purification, 29.4 mg (32.9fimol, 44%) of the title compound A as well as 9.7 mg (10.9 (imol, 14%) of the title compound B are isolated. 'H-NMR (CDC13) of A: 8 = 1.03 (3H), 1.13 (3H), 1.15 (3H), 1.23 (IH), 1.31 (3H), 1.34-2.74 (17H), 2.78 (3H), 2.86 (IH), 3.44 (IH), 3.67 (3H), 4.46 (IH), 4.67 (IH), 5.01 (IH), 5.05 (IH), 5.46 (IH), 5.70 (IH), 6.08 (IH), 6.72 (2H), 7.01 (IH), 7.08 (IH), 7.16 (IH), 7.31 (IH), 7.77 (IH), 7.92 (IH) ppm. Example EL44 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l -yl)-hexanoic acid 4-(4S,7R,8S,9S, 13Z, 16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Example EL44a 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example EL12b, 329 mg (467 pmol) of the compound prepared according to Example EL 12a are reacted with 821 mg of the compound prepared according to Example L16. After working-up and purification, 120 mg (118 jimol, 25%) of the title compound are isolated. WO 2004/012735 PCT/EP2003/008483 83 Example EL44 6-(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-hexanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-aIlyI-8-hydroxy-5,5,9,13-tetramethyM6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example ELI, 120 mg (118 (imol) of the compound prepared according to Example EL44a are reacted. After working-up and purification, 60 mg (66 |amol, 56%) of the title compound are isolated. !H-NMR (CDCla): 8 « 1.01 (3H), 1.05 (IH), 1.13 (3H), 1.14 (3H), 1.33-1.89 (12H), 1.71 (3H), 2.24-2.70 (8H), 2.74 (3H), 3.00 (IH), 3.40 (IH), 3.55 (2H), 3.69 (IH), 4.49 (IH), 4.71 (IH), 5.00 (IH), 5.05 (IH), 5.18 (IH), 5.56 (IH), 5.71 (IH), 5.99 (IH), 6.70 (2H), 6.95 (IH), 7.03 (IH), 7.11 (IH), 7.37 (IH), 7.75 (IH), 7.95 (IH), ppm. Example EL45 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(lS,3S,7S,10R,llS,12S, 16R)-[10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-chloro-phenyl ester (A) and 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(1R,3S,7S,10R,11S,12S, 16S)-[10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0Jheptadec-7-yloxycarbonyloxymethyl]-2-chloro-phenyl ester (B) Analogously to Example EL2,60 mg (66 (jimol) of the compound prepared according to Example EL44 is reacted. After working-up and purification, 32 mg (34.7 (imol, 53%) of the title compound A as well as 11 mg (11.9 p-mol, 18%) of the title compound B are isolated. *H-NMR (CDCla) von A: 8 = 1.02 (3H), 1.14 (3H), 1.15 (3H), 1.24 (IH), 1.32 (3H), 1.34-2.74 (21H), 2.77 (3H), 2.86 (IH), 3.44 (IH), 3.55 (2H), 3.69 (IH), 4.46 (IH), 4.67 (IH), 5.01 (IH), 5.05 (IH), 5.46 (IH), 5.70 (IH), 6.09 (IH), 6.69 (2H), 6.99 (IH), 7.04 (IH), 7.16 (IH), 7.32 (IH), 7.77 (IH), 7.92 (IH) ppm. Example EL46 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chloro-phenyl ester WO 2004/012735 PCT/EP2003/008483 84 Example EL46a 11 -(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-(tert-butyl-dimethy l-silanyloxy)-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example EL12b, 323 mg (459 (nmol) of the compound prepared according to Example EL12a are reacted with 790 mg of the compound prepared according to Example L17. After working-up and purification, 96 mg (88 nmol, 19%) of the title compound are isolated. Example EL46 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-8-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl]-2-chlor-phenyl ester Analogously to Example ELI, 59 mg (54 |amol) of the compound prepared according to Example EL46a are reacted. After working-up and purification, 27 mg (27.7 nmol, 51%) of the title compound are isolated. 'H-NMR (CDCI3): 5 = 1.01 (3H), 1.13 (3H), 1.15 (3H), 1.23-2.70 (31H), 1.71 (3H), 2.74 (3H), 2.99 (IH), 3.40 (IH), 3.51 (2H), 3.68 (IH), 4.49 (IH), 4.70 (IH), 5.00 (IH), 5.04 (IH), 5.18 (IH), 5.56 (IH), 5.71 (IH), 5.99 (IH), 6.68 (2H), 6.95 (IH), 7.03 (IH), 7.11 (IH), 7.36 (IH), 7.75 (IH), 7.95 (IH) ppm. Example EL47 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(lS,3S,7S,10R,l 1S,12S, 16R)-[10-allyHl-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-chloro-phenyl ester (A) and ll-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(1R,3S,7S,10R,11S, 12S, 16S)-[10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-chloro-phenyl ester (B) Analogously to Example EL2,27 mg (27 nmol) of the compound prepared according to Example EL46 are reacted. After working-up and purification, 14 mg (14.1 |j.mol, WO 2004/012735 PCT/EP2003/008483 85 52%) of the title compound A as well as 5 mg (5.0 (imol, 19%) of the title compound B are isolated. 'H-NMR (CDCb) of A: 8 = 1.02 (3H), 1.13 (3H), 1.15 (3H), 1.19-1.84 (27H), 2.09-2.74 (8H), 2.77 (3H), 2.85 (IH), 3.44 (IH), 3.50 (2H), 3.69 (IH), 4.46 (IH), 4.67 (IH), 5.01 (IH), 5.06 (IH), 5.45 (IH), 5.70 (IH), 6.08 (IH), 6.68 (2H), 6.99 (IH), 7.04 (IH), 7.16 (IH), 7.31 (IH), 7.76 (IH), 7.91 (IH) ppm. Example EL48 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l -yl)-butanoic acid 4-(4S,7R,8S,9S, 13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Example EL48a 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(4S,7R,8S,9S, 13Z,16S)-[7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example EL12b, 340 mg (482 fimol) of the compound prepared according to Example EL14a are reacted with 885 mg of the compound prepared according to Example L15. After working-up and purification, 151 mg (152 nmol, 32%) of the title compound are isolated. Example EL48 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(4S,7R,8S,9S,13Z, 16S)-[7-allyl-4-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example ELI, 151 mg (152 jimol) of the compound prepared according to Example EL48a are reacted. After working-up and purification, 46 mg (52 jimol, 34%) of the title compound are isolated. to-NMR (CDCI3): 8 = 1.02 (3H), 1.07 (3H), 1.26 (3H), 1.71 (3H), 1.15-2.44 (13H), 2.51 (2H), 2.65 (2H), 2.84 (3H), 2.91 (IH), 3.55 (IH), 3.68 (2H), 3.99 (IH), 4.92 (IH), 4.98 (IH), 5.06-5.25 (4H), 5.70 (IH), 5.83 (IH), 6.72 (2H), 7.17 (IH), 7.31 (IH), 7.34 (IH), 7.49 (IH), 7.80 (IH), 7.96 (IH) ppm. WO 2004/012735 PCT/EP2003/008483 86 Example EL49 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(lS,3S,7S,10R,l 1S,12S, 16R)-[ 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5 -yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-l 1 -yloxycarbonyloxymethyl]-2-chloro-phenyl ester (A) and 4-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-butanoic acid 4-(1 R,3 S,7S, 1 OR, 11S, 12S, 16S)-[ 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-chloro-phenyl ester (B) Analogously to Example EL2, 46 mg (52 (Jimol) of the compound prepared according to Example EL48 are reacted. After working-up and purification, 6 mg (6.7 jimol, 13%) of the title compound A as well as 1 mg (1.1 jimol, 2%) of the title compound B are isolated. 'H-NMR (CDCla) of A: 8 = 0.97 (3H), 1.04 (3H), 1.24 (3H), 1.30 (3H), 1.14-2.76 (21H), 2.85 (3H), 3.68 (3H), 4.09 (IH), 4.23 (IH), 4.91 (IH), 4.97 (IH), 5.11 (2H), 5.22 (IH), 5.72 (IH), 6.25 (IH), 6.72 (2H), 7.16 (IH), 7.30 (IH), 7.37 (IH), 7.48 (IH), 7.83 (IH), 7.99 (IH) ppm. Example EL50 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoicacid4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Example EL50a 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example ELI 2b, 340 mg (482 jtmol) of the compound prepared according to Example EL14a are reacted with 848 mg of the compound prepared according to Example L16. After working-up and purification, 158 mg (155 jimol, 32%) of the title compound are isolated. WO 2004/012735 PCT/EP2003/008483 87 Example EL50 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoicacid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example ELI, 158 mg (155 (imol) of the compound prepared according to Example EL50a are reacted. After working-up and purification, 58 mg (64 (imol, 41%) of the title compound are isolated. 'H-NMR (CDC13): 8 = 1.02 (3H), 1.08 (3H), 1.22 (3H), 1.71 (3H), 0.90-2.45 (17H), 2.51 (2H), 2.61 (2H), 2.83 (3H), 2.88 (IH), 3.55 (3H), 3.97 (IH), 4.92 (IH), 4.98 (IH), 5.10-5.25 (4H), 5.71 (IH), 5.83 (IH), 6.69 (2H), 7.12 (IH), 7.30 (IH), 7.34 (IH), 7.49 (IH), 7.79 (IH), 7.95 (lH)ppm. Example EL51 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l--yl)-hexanoic acid 4-(lS,3S,7S,10R,l 1S,12S, 16R)- [10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo- 4,17-dioxa-bicyclo[ 14.1.0]heptadec-11 -yloxycarbonyloxymethyl]-2-chloro-phenyl ester (A) and 6-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoic acid 4- (1 R,3 S,7S, 1 OR, 11S, 12S, 16S)-[ 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl- benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0Jheptadec-ll- yloxycarbonyloxymethyl]-2-chloro-phenyl ester (B) Analogously to Example EL2, 58 mg (64 (imol) of the compound prepared according to Example EL50 are reacted. After working-up and purification, 25 mg (27 (imol, 42%) of the title compound A as well as 7 mg (7.6 jimol, 12%) of the title compound B are isolated. *H-NMR (CDCI3) of A: 8 = 0.97 (3H), 1.04 (3H), 1.24 (3H), 1.31 (3H), 1.12-2.65 (21H), 2.72 (IH), 2.84 (3H), 3.55 (2H), 3.71 (IH), 4.08 (IH), 4.22 (IH), 4.91 (IE), 4.96 (IH), 5.12 (2H), 5.23 (IH), 5.72 (IH), 6.24 (IH), 6.69 (2H), 7.13 (IH), 7.30 (IH), 7.37 (IH), 7.48 (IH), 7.83 (IH), 7.97 (IH) ppm. Example EL52 1 l-(2s5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester WO 2004/012735 PCT/EP2003/008483 Example EL52a 11 -(2,5-Dioxo-2,5-dihydro-pyrrol-1 -yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-ally l-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example EL 12b, 355 mg (476 jimol) of the compound prepared according to Example EL14a are reacted with 790 mg of the compound prepared according to Example L17. After working-up and purification, 122 mg (112 jumol, 24%) of the title compound are isolated. Example EL52 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(4S,7R,8S,9S,13Z,16S)-[7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example ELI, 122 mg (112 pmol) of the compound prepared according to Example EL52a are reacted. After working-up and purification, 28 mg (29 (imol, 26%) of the title compound are isolated. 'H-NMR (CDCI3): 8 = 1.02 (3H), 1.08 (3H), 1.22 (3H), 1.11-2.48 (26H), 1.71 (3H), 2.51 (2H), 2.61 (2H), 2.83 (3H), 2.89 (IH), 3.46-3.58 (3H), 3.98 (IH), 4.61 (2H), 4.92 (IH), 4.98 (IH), 5.11-5.25 (3H), 5.70 (IH), 5.83 (IH), 6.68 (2H), 7.00 (IH), 7.18 (IH), 7.29 (IH), 7.36 (IH), 7.79 (IH), 7.95 (IH) ppm. Example EL53 1 l-(2,5-Dioxo-2,5-dihydro-pyrrol-l -yl)-undecanoic acid 4-(l S,3S,7S,10R, 11S,12S, 16R)-[10-allyl-7-hydroxy-8,8,l 2,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1,0]heptadec-l l-yloxycarbonyloxymethyl]-2-chloro-phenyl ester (A) and ll-(2,5-Dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoic acid 4-(1 R,3 S,7S, 1 OR, 11S, 12S, 16S)-[ 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-chloro-phenyl ester (B) Analogously to Example EL2, 28 mg (29 (imol) of the compound prepared according to Example EL52 are reacted. After working-up and purification, 6.2 mg (6.3 (imol, WO 2004/012735 PCT/EP2003/008483 89 22%) of the title compound A as well as 0.3 mg (0.3 jimol, 1%) of the title compound B are isolated. 'H-NMR (CDCI3) of A: 8 = 0.97 (3H), 1.04 (3H), 1.23 (3H), 0.82-1.83 (25H), 2.16 (2H), 2.24-2.65 (7H), 2.72 (IH), 2.84 (3H), 3.50 (2H), 3.70 (IH), 4.08 (IH), 4.21 (IH), 5 4.92 (IH), 4.97 (IH), 5.11 (2H), 5.22 (IH), 5.72 (IH), 6.25 (IH), 6.67 (2H), 7.12 (IH), 7.30 (IH), 7.37 (IH), 7.49 (IH), 7.83 (IH), 7.98 (IH) ppm. Example EL54 (4S,7R,8S,9S, 13Z,16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-10 methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-1 -yl)-3-nitro-butyrylamino]-benzyl ester Example EL54a (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-15 5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-l 3-en-4-yl ester 4-amino-benzyl ester Analogously to Example EL 12b, 160 mg (227 jimol) of the compound prepared according to Example EL12a are reacted with 191 mg (4-amino-3-nitro-phenyl)-methanol. After working-up and purification, 51 mg (61 (imol, 27%) of the title 20 compound are isolated. 'H-NMR (CDC13): 8 - 0.07 (3H), 0.12 (3H), 0.92 (9H), 0.99 (3H), 1.03 (3H), 1.23 (3H), 0.85-1.74 (8H), 1.93 (IH), 2.28 (IH), 2.38 (2H), 2.49 (IH), 2.66 (IH), 2.77 (3H), 2.82 (IH), 2.97 (IH), 3.22 (IH), 3.87 (IH), 4.85-5.03 (4H), 5.22 (IH), 5.42 (IH), 5.74 (IH), 5.89 (IH), 6.10 (2H), 6.68 (IH), 7.19 (IH), 7.32 (IH), 7.73 (IH), 7.90 (IH), 7.98 25 (IH) ppm. Example EL54b (4S,7R,8S,9S,13Z,16S)-Carbonicacid7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-30 en-4-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-butyrylamino]-3-nitro-benzyl ester 153 mg (837 |imol) of the compound prepared according to Example L4 are mixed with 1.82 ml thionyl chloride and refluxed for 3.5 hours. The mixture is diluted with WO 2004/012735 PCT/EP2003/008483 90 toluene and evaporated. A solution of 130 mg (156 jimol) of the compound prepared according to Example 54a in 6 ml dichloromethane is added, 75 (al pyridine are admixed, and the mixture is stirred at 23 °C for 16 hours. It is poured into water, extracted several times with dichloromethane, the combined organic extracts are 5 washed with water and dried over sodium sulfate. After filtration and removal of the solvent, the residue is purified by chromatography. 101 mg(101 jimol, 65%) of the title compound are isolated. Example EL54 10 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-butyrylamino]-3-nitro-benzyl ester Analogously to Example ELI, 101 mg (101 (imol) of the compound prepared according to Example EL54a are reacted. After working-up and purification, 62 mg 15 (70 jimol, 69%) of the title compound are isolated. 'H-NMR (CDCI3): 8 = 1.01 (3H), 1.14 (6H), 1.39 (2H), 1.64 (2H), 1.71 (3H), 1.80 (2H), 2.07 (2H), 2.23-2.54 (8H), 2.69 (IH), 2.77 (3H), 2.96 (IH), 3.39 (IH), 3.65 (2H), 3.69 (IH), 4.52 (IH), 4.75 (IH), 5.00 (IH), 5.05 (IH), 5.18 (IH), 5.55 (IH), 5.71 (IH), 5.98 (IH), 6.71 (2H), 7.31 (IH), 7.36 (IH), 7.77 (IH), 7.91 (IH), 7.93 (IH), 8.67 (IH), 20 10.28 (IH) ppm. Example EL55 (1S,3S,7S,10R,11S,12S,16R)-Carbonic acid 10-allyl-l 1-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-25 bicyclo[14.1.0]heptadec-7-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)- butyrylamino]-3-nitro-benzyl ester (A) and (1R,3S,7S,10R,11S,12S,16S)-Carbonic acid 10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-1 -yl)-butyrylamino] -3 -nitro-benzyl ester (B) 30 Analogously to Example EL2, 62 mg (70 jimol) of the compound prepared according to Example EL54 are reacted. After working-up and purification, 38 mg (42 jimol, 60%) of the title compound A as well as 11 mg (12 jimol, 17%) of the title compound B are isolated. WO 2004/012735 PCT/EP2003/008483 10 91 'H-NMR (CDC13) of A: S = 1.03 (3H), 1.13 (3H), 1.17 (3H), 1.32 (3H), 1.20-2.58 (17H), 2.70 (IH), 2.79 (3H), 2.85 (IH), 3.43 (IH), 3.65 (2H), 3.69 (IH), 4.52 (IH), 4.72 (IH), 5.01 (IH), 5.05 (IH), 5.45 (IH), 5.70 (IH), 6.07 (IH), 6.71 (2H), 7.31 (IH), 7.35 (IH), 7.78 (IH), 7.88 (IH), 7.95 (IH), 8.68 (IH), 10.28 (IH) ppm. Example EL56 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5 -yl)-2,6-dioxo-oxacyclohexadec-13 -en-4-yl ester 4-[6-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoylamino]-3-nitro-benzyl ester Example EL56a (4S,7R,8S,9S,13Z,16S)-Carbonicacid7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-[6-(2,5-dioxo-2,5-dihydro-pyrrol-l -yl)-hexanoylamino]-3-nitro-benzyl 15 ester Analogously to Example EL54bs 50 mg (60 jimol) of the compound prepared according to Example EL54a are reacted with the compound prepared according to Example L5. After working-up and purification, 58 mg (56 p.mol, 94%) of the title compound are isolated. 20 Example EL56 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-[6-(2,5-dioxo-2,5-dihydro-pyrrol-l -yl)-hexanoylamino]-3-nitro-benzyl ester 25 Analogously to Example ELI, 82 mg (80 (omol) of the compound prepared according to Example EL56a are reacted. After working-up and purification, 34 mg (37 jxmol, 46%) of the title compound are isolated. 'H-NMR (CDCI3): 8 = 1.01 (3H), 1.14 (6H), 1.70 (3H), 1.31-2.57 (20H), 2.69 (IH), 2.78 (3H), 2.97 (IH), 3.39 (IH), 3.54 (2H), 3.69 (IH), 4.51 (IH), 4.74 (IH), 5.00 (IH), 30 5.05 (IH), 5.18 (IH), 5.55 (IH), 5.78 (IH), 5.98 (IH), 6.69 (2H), 7.31 (IH), 7.36 (IH), 7.76 (IH), 7.92 (IH), 7.93 (IH), 8.71 (IH), 10.32 (IH) ppm. Example EL57 WO 2004/012735 PCT/EP2003/008483 92 (1S,3S,7S,10R,11S, 12S, 16R)-Carbonic acid 10-allyl-l 1-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-[6-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoylamino]-3-nitro-benzyl ester (A) and (1 R,3 S,7S, 1 OR, 11S, 12S, 16S)-Carbonic 5 acid 10-allyl-l 1-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-[6-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoylamino]-3-nitro-benzyl ester (B) Analogously to Example EL2, 34 mg (37 jimol) of the compound prepared according to Example EL56 are reacted. After working-up and purification, 19 mg (20.4 jiimol, 10 55%) of the title compound A as well as 6 mg (6.4 (imol, 17%) of the tide compound B are isolated. JH-NMR (CDCI3) of A: 8 = 1.02 (3H), 1.14 (3H), 1.15 (3H), 1.39 (2H), 1.70 (3H), 1.65 (2H), 1.80 (2H), 2.06 (2H), 2.23-2.55 (8H), 2.69 (IH), 2.77 (3H), 2.97 (IH), 3.39 (IH), 3.65 (2H), 3.69 (IH), 4.52 (IH), 4.75 (IH), 5.00 (IH), 5.05 (IH), 5.18 (IH), 5.55 15 (IH), 5.71 (IH), 5.97 (IH), 6.71 (2H), 7.31 (IH), 7.36 (IH), 7.76 (IH), 7.91 (IH), 7.93 (IH), 8.68 (IH), 10.28 (lH)ppm. Example EL58 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-[l l-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoylamino]-3-nitro-benzyl ester Example EL58a (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-25 5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-[l l-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoylamino]-3-nitro-benzyl ester Analogously to Example EL54b, 130 mg (156 (imol) of the compound prepared according to Example EL54a are reacted with the compound prepared according to 30 Example L6. After working-up and purification, 120 mg (109 nmol, 70%) of the title compound are isolated. Example EL58 WO 2004/012735 PCT/EP2003/008483 93 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 4-[l l-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoylamino3-3-nitro-benzyl ester Analogously to Example ELI, 120 mg (109 (imol) of the compound prepared according to Example EL58a are reacted. After working-up and purification, 89 mg (90 jimol, 83%) of the title compound are isolated. JH-NMR (CDCls): 5 = 1.01 (3H), 1.13 (3H), 1.14 (3H), 1.70 (3H), 1.04-2.56 (30H), 2.69 (IH), 2.78 (3H), 2.97 (IH), 3.39 (IH), 3.50 (2H), 3.69 (IH), 4.52 (IH), 4.74 (IH), 5.01 (IH), 5.05 (IH), 5.18 (IH), 5.55 (IH), 5.71 (IH), 5.97 (IH), 6.67 (2H), 7.31 (IH), 7.36 (IH), 7.76 (IH), 7.91 (IH), 7.93 (IH), 8.72 (IH), 10.33 (IH) ppm. Example EL59 (1S,3S,7S,10R,11S,12S,16R)-Carbonic acid 10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-[l l-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoylamino]-3-nitro-benzyl ester (A) and (1R,3S,7S,10R,11S,12S,16S)-Carbonic acid 10-allyl-l 1-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-[ll-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-undecanoylamino]-3-nitro-benzyl ester (B) Analogously to Example EL2, 89 mg (90 (imol) of the compound prepared according to Example EL58 are reacted. After working-up and purification, 45 mg (jimol, %) of the title compound A as well as 15 mg (|imol, %) of the title compound B are isolated. 'H-NMR (CDCIs) of A: S = 1.03 (3H), 1.13 (3H), 1.16 (3H), 1.20-1.83 (26H), 2.09-2.57 (8H), 2.72 (IH), 2.79 (3H), 2.86 (IH), 3.44 (IH), 3.50 (2H), 3.69 (IH), 4.51 (IH), 4.72 (IH), 5.01 (IH), 5.05 (IH), 5.45 (IH), 5.71 (IH), 6.08 (IH), 6.68 (2H), 7.32 (IH), 7.35 (IH), 7.78 (IH), 7.88 (IH), 7.96 (IH), 8.73 (IH), 10.33 (IH) ppm. Example EL60 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 6-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-hexyl ester WO 2004/012735 PCT/EP2003/008483 94 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-8-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-l 6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-l 3-en-4-yl ester 6-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-hexyl ester Analogously to Example EL12b, 1.25 g (1.77 mmol) of the compound prepared according to Example EL12a are reacted with 1.75 g of the compound prepared according to L18. After working-up and purification, 119 mg (138 [imol, 8%) of the title compound are isolated. Example EL60 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-8-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-4-yl ester 6-(2,5-dioxo-2,5-dihydro-pyrrol-1 -yl)-hexyl ester Analogously to Example ELI, 101 mg (117 junol) of the compound prepared according to Example EL60a are reacted. After working-up and purification, 68 mg (91 jimol, 77%) of the title compound are isolated. 'H-NMR (CDC13): 8 = 1.02 (3H), 1.12-1.87 (19H), 1.70 (3H), 2.23-2.56 (6H), 2.66 (IH), 2.83 (3H), 2.97 (IH), 3.40 (2H), 3.48 (2H), 3.68 (IH), 3.75 (IH), 5.01 (IH), 5.05 (IH), 5.17 (2H), 5.51 (IH), 5.72 (IH), 5.97 (IH), 6.68 (2H), 7.35 (IH), 7.78 (IH), 7.92 (lH)ppm. Example EL61 (1S,3S,7S,10R,11 S,12S,16R)-Carbonic acid 10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 6-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-hexyl ester (A) and (1R,3S,7S,10R,1 lS,12S,16S)-Carbonic acid 10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa- bicyclo[14.1.0]heptadec-7-yl ester 6-(2,5-dioxo-2,5-dihydro-pyrrol-l -yl)-hexyl ester (B) Analogously to Example EL2, 68 mg (91 jimol) of the compound prepared according to Example EL60 are reacted. After working-up and purification, 26 mg (34 jimol, 37%) of the title compound A as well as 10 mg (13 jimol, 14%) of the title compound B are isolated. WO 2004/012735 PCT/EP2003/008483 95 'H-NMR (CDCI3) of A: 5 = 1.03 (3H), 1.14 (3H), 1.18 (3H), 1.32 (3H), 1.10-1.85 (15H), 2.11-2.43 (5H), 2.52 (IH), 2.70 (IH), 2.84 (3H), 2.86 (IH), 3.38-3.51 (4H), 3.69 (IH), 3.74 (IH), 5.01 (IH), 5.05 (IH), 5.42 (IH), 5.72 (IH), 6.07 (IH), 6.69 (2H), 7.32 (IH), 7.80 (IH), 7.90 (IH) ppm. 5 Example EL62 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-4-hydroxy-5,5,9,13-tetramethyl-l6-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-3-nitro-butyrylamino]-benzyl ester 10 Example EL62a (4S,7R,8S,9S,13Z,16S)-Carbonicacid7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 4-amino-benzyl ester 15 Analogously to Example EL12b, 1.73 g (2.46 mmol) of the compound prepared according to Example EL14a are reacted with 2.06 g (4-amino-3-nitro-phenyl)-methanol. After working-up and purification, 420 mg (502 famol, 20%) of the title compound are isolated. JH-NMR (CDCI3): 5 = -0.10 (3H), 0.09 (3H), 0.84 (9H), 0.96-1.21 (2H), 1.01 (3H), 20 1.12 (3H), 1.15 (3H), 1.70 (3H), 1.61-1.85 (4H), 2.11 (IH), 2.29 (2H), 2.54-2.78 (3H), 2.83 (3H), 2.90 (IH), 3.31 (IH), 3.93 (IH), 4.86 (IH), 4.96 (IH), 5.04 (IH), 5.11 (IH), 5.25 (2H), 5.55 (IH), 5.72 (IH), 6.14 (2H), 6.82 (IH), 7.35 (IH), 7.43 (IH), 7.79 (IH), 7.91 (IH), 8.18 (IH) ppm. 25 Example EL62b (4S,7R,8S,9S,13Z,16S)-Carbonicacid7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-butyrylamino]-3-nitro-benzyl ester 30 Analogously to Example EL54b, 140 mg (167 |imol) of the compound prepared according to Example EL62a are reacted with the compound prepared according to Example L4. After working-up and purification, 150 mg (150 (junol, 90%) of the title compound are isolated. WO 2004/012735 PCT/EP2003/008483 96 Example EL62 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-3-nitro-butyrylamino]-benzyl ester Analogously to Example ELI, 145 mg (145 (imol) of the compound prepared according to Example EL62a are reacted. After working-up and purification, 67 mg (76 (imol, 52%) of the title compound are isolated. 'H-NMR (CDCI3): 6 = 1.02 (3H), 1.08 (3H), 1.22 (3H), 1.70 (3H), 1.09-2.12 (8H), 2.27-2.55 (8H), 2.83 (3H), 2.87 (2H), 3.56 (IH), 3.65 (2H), 3.99 (IH), 4.93 (IH), 4.98 (IH), 5.12-5.26 (4H), 5.71 (IH), 5.83 (IH), 6.70 (2H), 7.33 (IH), 7.67 (IH), 7.79 (IH), 7.94 (IH), 8.25 (IH), 8.79 (IH), 10.32 (IH) ppm. Example EL63 (1S,3S,7S,10R,1 lS,12S,16R)-Carbonic acid 10-allyI-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1.0]heptadec-11 -yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-butyrylamino]-3-nitro-benzyl ester (A) and (1R,3S,7S,10R,11S,12S,16S)-Carbonic acid 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-l 1-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-butyrylamino]-3-nitro-benzyl ester (B) Analogously to Example EL2, 67 mg (76 (imol) of the compound prepared according to Example EL62 are reacted. After working-up and purification, 37 mg (41 jimol, 54%) of the title compound A as well as 12 mg (13 (imol, 18%) of the title compound B are isolated. Example EL64 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13-en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-3-nitro-hexanoylamino]-benzyl ester WO 2004/012735 PCT/EP2003/008483 97 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)- hexanoylamino]-3-nitro-benzyl ester Analogously to Example EL54b, 140 mg (167 {imol) of the compound prepared according to Example EL62a are reacted with the compound prepared according to Example L5. After working-up and purification, 155 mg (150 |imol, 90%) of the title compound are isolated. Example EL64 (4S,7R,8S,9S, 13Z, 16S)-Carbonic acid 7-allyl-4-hydroxy-5,5,9,13 -tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-3-nitro-hexanoylamino]-ben2yl ester Analogously to Example ELI, 150 mg (151 jimol) of the compound prepared according to Example EL64a are reacted. After working-up and purification, 68 mg (74 |imol, 49%) of the title compound are isolated. 'H-NMR (CDC13): 5 = 1.02 (3H), 1.07 (3H), 1.23 (3H), 1.70 (3H), 1.16-2.54 (20H), 2.84 (3H), 2.87 (2H), 3.54 (3H), 3.98 (IH), 4.92 (IH), 4.98 (IH), 5.13-5.26 (4H), 5.71 (IH), 5.83 (IH), 6.68 (2H), 7.33 (IH), 7.67 (IH), 7.79 (IH), 7.94 (IH), 8.26 (IH), 8.82 (IH), 10.37 (lH)ppm.58 Example EL65 (1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-Carbonic acid 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pym>l-l-yl)- hexanoylamino]-3-nitro-benzyl ester (A) and (1R,3S,7S,10R,11S,12S,16S)-Carbonic acid 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-l 1-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-hexanoylamino]-3-nitro-ben2yl ester (B) Analogously to Example EL2, 68 mg (74 jimol) of the compound prepared according to Example EL64 are reacted. After working-up and purification, 44 mg (47 jimol, 64%) of the title compound A as well as 3 mg (3 (imol, 4%) of the title compound B are isolated. WO 2004/012735 PCT/EP2003/008483 98 Example EL66 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl-4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-13 -en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-3-nitro-undecanoylamino]-ben2yl ester Example EL66a (4S,7R,8S,9S,13Z, 16S)-Carbonic acid 7-allyl-4-(tert-butyl-dimethyl-silanyloxy)-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-l 3-en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)- undecanoylamino]-3-nitro-benzyl ester Analogously to Example EL54b, 140 mg (167 (imol) of the compound prepared according to Example EL62a are reacted with the compound prepared according to Example L6. After working-up and purification, 165 mg (150 (imol, 90%) of the title compound are isolated. Example EL66 (4S,7R,8S,9S,13Z,16S)-Carbonic acid 7-allyl~4-hydroxy-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-2,6-dioxo-oxacyclohexadec-l 3-en-8-yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-3-nitro-undecanoylamino]-benzyl ester Analogously to Example ELI, 145 mg (132 |imol) of the compound prepared according to Example EL66a are reacted. After working-up and purification, 106 mg (108 (imol, 82%) of the title compound are isolated. 'H-NMR (CDC13): 8 = 1.01 (3H), 1.06 (3H), 1.24 (3H), 1.70 (3H), 1.14-2.57 (30H), 2.82 (3H), 2.89 (2H), 3.50 (2H), 3.55 (IH), 4.01 (IH), 4.92 (IH), 4.99 (IH), 5.11-5.28 (4H), 5.70 (IH), 5.83 (IH), 6.69 (2H), 7.34 (IH), 7.67 (IH), 7.79 (IH), 7.96 (IH), 8.26 (IH), 8.85 (IH), 10.38 (IH) ppm. Example EL67 (1S,3S,7S,10R,1 lS,12S,16R)-Carbonic acid 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[l 4.1.0]heptadec-l 1 -yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)- undecanoylamino]-3-nitro-benzyl ester (A) and (1R,3S,7S,10R,11S,12S,16S)-Carbonic acid 10-allyl-7 -hydroxy-8,8,12,16- WO 2004/012735 PCT/EP2003/008483 99 tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1.0]heptadec-11 -yl ester 4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-1 -yl)-undecanoylamino]-3-nitro-benzyl ester (B) Analogously to Example EL2, 106 mg (108 |imol) of the compound prepared 5 according to Example EL66 are reacted. After working-up and purification, 58 mg (58 jumol, 54%) of the title compound A as well as 6 mg (6 |imol, 6%) of the title compound B are isolated. 'H-NMR (CDCls) of A: 8 = 0.96 (3H), 1.04 (3H), 1.23 (3H), 1.31 (3H), 0.81-1.83 (23H), 2.16 (2H), 2.23-2.66 (6H), 2.71 (IH), 2.85 (3H), 3.5 (2H), 3.72 (IH), 4.08 (IH), 10 4.24 (IH), 4.92 (IH), 4.97 (IH), 5.15 (2H), 5.22 (IH), 5.72 (IH), 6.25 (IH), 6.68 (2H), 7.36 (IH), 7.66 (IH), 7.83 (IH), 7.97 (IH), 8.25 (IH), 8.83 (IH), 10.37 (IH) ppm. WO 2004/012735 PCT/EP2003/008483 100 Examples of the Synthesis of Effector-Linker Recognition Units (ELE) Example ELE1 [3 -(3-(AP3 9r)-Sulfanyl-2,5-dioxo-pyrrolidin-1 -yl)-propyl] -carbamic acid-10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester Example ELE la Reduction of an Antibody Fragment with Terminal Cysteine A single-strand protein that consists of the variable domains of the heavy and light antibody chains (single-chain Fv, scFv) of the amino acid sequence EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAPGKGLEWVSSISG SSGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKPFPYFDY WGQGTLVTVSSGDGSSGGSGGASEIVLTQSPGTLSLSPGERATLSCRASQSVSS SFLAWYQQKPGQAPRLLIYYASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV YYCQQTGRIPPTFGQGTKVEIKGGGCA, which specifically recognizes the fibronectin domain B (ED-B) and is referred to as AP39, is used for coupling after reduction of the c-terminal cysteine. For reduction, the solution of 661 jig of tri(2-carboxyethyl)phosphine-hydrochloride in 236 fil of PBS is mixed with the solution of 1.54 mg of AP39 in 1.12 ml of PBS, and it is incubated for 1.5 hours at 25°C. Desalination is done with a pre-equilibrated NAP-5 column at a concentration of450 (il of AP39r and 50 (J.1 of PBS. After elution with 1 ml of PBS, the reduced antibody fragment AP39r is isolated in a concentration of 0.7 mg/ml. Example ELE1 (1 S,3S,7S(3RS), 1 OR, 11S, 12S, 16R)-[3-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-propyl]-carbamic acid-10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1.0]heptadec-7-yl ester 22.5 |xl of a 1.38 mmol solution of effector-linker conjugate A in DMSO, prepared according to Example EL2, is added to 400 |il of the solution, prepared according to Example ELEla, of the reduced antibody fragment, mixed with 77.5 (4-1 of PBS and incubated at 25°C for 1 hour. Desalination is done with a pre-equilibrated WO 2004/012735 PCT/EP2003/008483 101 NAP5 column at a concentration of 500 jlxI of the reaction solution. After elution with PBS, the solution of the title compound is isolated The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26203.1 m/z (exp.): 26218 ± 20 Example ELE2 (1 S,3S,7S(3RS), 10R, 1 lS,12S,16R)-[5-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-pentyl]-carbamic acid-10-allyl-l 1 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[l 4.1.0]heptadec-7-yl ester Analogously to Example ELE1, the antibody ftagment that is reduced according to Example ELE la is reacted with effector-linker conjugate A that is prepared according to Example EL4, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26231.2 m/z (exp.): 26236 ± 20 Example ELE3 (lS,3S,7S(3RS),10R,llS,12S,16R)-[10-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-decyl]-carbamic acid-10-allyl-l 1 -hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[ 14.1.0]heptadec-7-yl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is prepared according to Example EL6, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26301.4 m/z (exp.): 26303 ± 20 Example ELE4 (lS,3S,7S,10R,llS(3RS),12S,16R)-[3-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-propyl]-carbamicacid-10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[l 4.1.0]heptadec-l 1 -yl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is prepared according to Example EL8, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. WO 2004/012735 PCT/EP2003/008483 102 m/z (Calc.): 26203.2 m/z (exp.): 26206 ± 20 Example ELE5 (1 S,3 S,7S, 1 OR, 11 S(3RS), 12S, 16R)-[5-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-1-yl)-pentyl]-carbamic acid-10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxabicyclo[14.1,0]heptadec-l 1-yl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is prepared according to Example EL 10, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26231.2 m/z (exp.): 26225 ± 20 Example ELE6 (lS,3S(E),7S,10R,llS,12S,16R)-[3-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-propyl]-carbamicacid-7-[3-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-propylcarbamoyloxy]-8,8,10,12,16-pentamethyl-3 -[1 -methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yl ester (A) and (lS,3S(E),7S,10R,llS,12S,16R)-[3-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-propyl]-carbamic acid-1 l-[3-(2,5-dioxo-2,5-dihydro-pyrrol-l-yl)-propylcarbamoyloxy]-8,8,10,12,16-pentamethyI-3-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester (B) Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate that is prepared according to Example ELI 1, and the solution of the title compounds is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. ' m/z (Calc.): 26347.3 m/z (exp.): 26358 ± 20 Example ELE7 (1 S,3 S(E),7 S, 1 OR, 11S, 12S, 16R)-N-[1 -({4-[2-(7,11 -Dihydroxy-8,8,10,12,16-pentamethyl-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-3-yl)-propenyl]-thiazol-2-ylmethyl}-carbamoyl)-ethyl]-3-(AP39r)-disulfanyl-N-methyl-propionamide Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is WO 2004/012735 PCT/EP2003/008483 103 prepared according to Example EL 16, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26173 m/z (exp.): 26174 ± 20 Example ELE8 (1 S,3 S(E),7S, 1 OR, 11S, 12S, 16R)-2-[Methyl-(3-(AP39r)-disulfanyl-propionyl)-amino]-propionic acid-4-[2-(7,11 -dihydroxy-8,8,10,12,16-pentamethyl-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1,0]heptadec-3-yl)-propenyl]-thiazol-2-ylmethyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is prepared according to Example EL 17, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26174 m/z (exp.): 26163 ± 20 Example ELE9 (1S,3S,7S,10R,11S,12S,16R)-Carbonic acid-10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is prepared according to Example EL 13, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26238 m/z (exp.): 26224 ± 20 Example ELE10 (lS,3S,7S,10R,llS,12S,16R)-Carbonicacid-10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yl ester 4-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is prepared according to Example EL15, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. WO 2004/012735 PCT/EP2003/008483 104 m/z (Calc.): 26238 m/z (exp.): 26243 ± 20 Example ELE11 4-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-butanoic acid 4-(lS,3S,7S,10R,l IS, 12S, 16R)-[10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4}17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is prepared according to Example EL19, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26383 m/z (exp.): 26377 ± 20 Example ELE12 4-(3-(AP39r)-Sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-butanoic acid 4-(1S,3S,7S,10R,11S,12S,16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1.0]heptadec-l 1 -yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with effector-linker conjugate A that is prepared according to Example EL25, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26383 m/z (exp.): 26381 ± 20 Example ELE13 6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexanoic acid 4-(1S, 3S,7S,10R, 11S, 12S,16R)-[10-allyI-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared WO 2004/012735 PCT/EP2003/008483 105 according to Example EL21, and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26411 m/z (exp.): 26384 ± 30 m/z (Calc.) : 25673 m/z (exp.): 25657 ± 20 (6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexanoic acid fragment) Example ELE 14 ll-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-undecanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[ 10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL23 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.) : 26482 m/z (exp.): 26477 ± 20 m/z (Calc.) : 25744 m/z (exp.): 26752 ± 20 (ll-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-undecanoic acid fragment) Example ELE 15 6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL27 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26411 m/z (exp.): 26398 ± 20 m/z (Calc.): 25673 m/z (exp.): 25665 ± 20 (6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexanoic acid fragment) Example ELE 16 WO 2004/012735 PCT/EP2003/008483 106 ll-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-undecanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[ 10-allyl-7-hydroxy-8,8,12,16-tetramethyl~3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-nitro-phenyl ester 5 Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL29 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26482 m/z (exp.): 26491 ± 20 m/z (Calc.) : 25744 m/z (exp.): 25757 ± 20 (ll-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-undecanoic acid fragment) Example ELE 17 4-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-butanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl] -phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL31 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26338 m/z (exp.): 26304 ± 30 Example ELE18 6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL33 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26366 m/z (exp.): 26347 ± 30 WO 2004/012735 107 PCT/EP2003/008483 Example ELE19 ll-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-undecanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[l 4.1.0]heptadec-7-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL35 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26437 m/z (exp.): 26412 ± 30 Example ELE20 4-(3-(AP39r)~sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-butanoic acid 4-(1S,3S57S,10R,11S,12S, 16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2~methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-l 1-yloxycarbonyloxymethyl]-2-nitro-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL37 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26338 m/z (exp.): 26338 ± 20 Example ELE21 6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexanoic acid 4-(1s,3s97s,10r,11s,12s, 16r)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL39 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26366 m/z (exp.): 26384 ± 30 WO 2004/012735 PCT/EP2003/008483 108 Example ELE22 ll-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-undecanoic acid 4-(1 S,3S,7S, 10R, 11 S,12S, 16R)-[10-allyl-7-hydroxy-8,8,12,l 6-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL41 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26437 m/z (exp.): 26421 ± 30 Example ELE23 4-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-butanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1,0]heptadec-7-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL43 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26373 m/z (exp.): 26358 ± 20 m/z (Calc.) : 25645 m/z (exp.): 25627 ± 20 (4-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-butanoic acid fragment) Example ELE24 6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexanoic acid 4-(1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-[ 10-allyl-11 -hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared WO 2004/012735 PCT/EP2003/008483 109 according to Example EL45 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26401 m/z (exp.): 26395 ± 20 Example ELE25 1 l-(3-(AP39r)-sulfanyl-2,5-dioxo-pyirolidin-l-yl)-undecanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[ 10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo~4,17-dioxa-bicyclo[14.1.0]heptadec-7-yloxycarbonyloxymethyl]-2-chlor-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL47 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.) : 26471 m/z (exp.): 26463 ± 20 Example ELE26 4-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-butanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-chloro-phenyl ester Analogously to Example ELE1, the antibody fragment that is' reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL49 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26373 m/z (exp.): 26341 ± 30 Example ELE27 6-(3-(AP39r)-sulfanyl-255-dioxo-pyrtolidin-l-yl)-hexanoic acid 4-(1S,3S,7S,10R,11S,12S, 16R)-[10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[ 14.1.0]heptadec-l 1 -yloxycarbonyloxymethyl]-2-chlor-phenyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared WO 2004/012735 PCT/EP2003/008483 110 according to Example EL51 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26401 m/z (exp.): 26391 ± 20 5 Example ELE28 ll-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-undecanoic acid 4-(1S ,3 S,7S, 1 OR, 11S, 12S, 16R)-[ 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-chlor-phenyl ester 10 Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL53 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.) : 26471 m/z (exp.): 26466 ± 20 15 Example ELE29 (1S,3S,7S,10R,1 lS,12S,16R)-Carbonic acid 10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-[4-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-20 yl)-butyrylamino]-3-nitro-benzyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL55 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. 25 m/z (Calc.) : 26337 m/z (exp.): ± 20 Example ELE30 (1S,3S,7S,10R,11S,12S,16R)-Carbonic acid 10-allyl-ll-hydroxy-8,8,12,16-tetramethyl-3 -(2-methyl-benzothiazol-5 -yl)-5,9-dioxo-4,17-dioxa-30 bicyclo[14.1.0]heptadec-7-yl ester 4-[6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexanoylamino]-3-nitro-benzyl ester Analogously to Example ELE1, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared WO 2004/012735 111 PCT/EP2003/008483 according to Example EL57 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26365 m/z (exp.): ± 20 Example ELE31 (1S,3S,7S,10R,1 lS,12S,16R)-Carbonic acid 10-allyl-l 1-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 4-[l l-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-undecanoylamino]-3-nitro-benzyl ester Analogously to Example ELEl, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL59 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26436 m/z (exp.): ± 20 Example ELE32 (1S,3S,7S,10R,11S,12S,16R)-Carbonic acid 10-allyl-l l-hydroxy-8,8,12,16-tetramethyl-3-(2~methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-7-yl ester 6-(3-(AP39r)-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-hexyl ester Analogously to Example ELEl, the antibody fragment that is reduced according to Example ELEla is reacted with the effector-linker conjugate A that is prepared according to Example EL61 and the solution of the title compound is isolated. The dilution factor relative to the antibody fragment is approximately 2.5. m/z (Calc.): 26246 m/z (exp.): ± 20 Example ELE33 4-(3-(2H8-Ab)x-sulfanyl-2,5-dioxo-pyrrolidin-l-yl)-butanoic acid 4-(1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-[ 10-allyl-7-hydroxy-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-5,9-dioxo-4,17-dioxa-bicyclo[14.1.0]heptadec-ll-yloxycarbonyloxymethyl]-2-nitro-phenyl ester 100 |al of a solution of the thionylated antibody prepared according to Example ELE33a (about 3 nmol, about 6 thiol groups) are mixed with 42.3 |d of a 1.1 mM </div>

Claims

<div class="application article clearfix printTableText" id="claims"> WO 2004/012735 112 PCT/EP2003/008483 solution of the effector-linker conjugate A prepared according to Example EL25 in PBS, and the mixture is incubated at 23 °C for 1 hour. Desalination is performed by using a pre-equilibrated NAP5 column with a loading of 150 nl of the reaction solution. After elution with PBS, the solution of the title compound is isolated. The 5 loading factor x of antibody 2H8-A in relation to effector-linker is about 1:4 to 1:5. Example ELE33a Thionylation of a complete immunoglobuline (IgG), e.g., the 2H8 antibody For the introduction of thionyl groups an amine-free solution of the 2H8 antibody in 10 phosphate buffer having a concentration in the range of about 1-10 mg/ml at a pH of 7.2 is mixed with the 10- to 100-fold excess of 2-iminothiolane and is allowed to react for 1 hour at 23 °C. The number of the introduced thiol groups is 1 to about 15 depending on the excess of reagent. WO 2004/012735 PCT/EP2003/008483 113 Claims:

1. Effector conjugate of general formula (I): in which Rla Rlb, independently of one another, are hydrogen, Cj-Cjo alkyl, aryl, aralkyl, or together a -(CH2)m group, in which m is 2 to 5, 10 R2a, R2b, independently of one another, are hydrogen, C i -C i q alkyl, aryl, aralkyl, or together a -(CH2)n group, in which n is 2 to 5, or C2-C10 alkenyl, or C2-C1Q alkynyl, R3 is hydrogen, Cj-Cio alkyl, aryl or aralkyl, and R4a, R4b independently of one another, are hydrogen, Cj-Cjo alkyl, aryl, ] 5 aralkyl, or together a -(CH2)p group, in which p is 2 to 5, r5 is hydrogen, Cj-Cjo alkyl, aryl, aralkyl, CO2H, C02alkyl, CH2OH, CH2Oalkyl, CH2Oacyl, CN, CH2NH2, CH2N(alkyl, acyl)1>2, or CH2Hal, Hal is a halogen atom, 20 R^, r7 in each case are hydrogen, or together an additional bond, or together an 13/12 2004 ION 17:57 FAX +49 89 21029633 df-mp Munich Schering 1011/011 114 oxygen atom, or together an NH group, or together an N-alkyl group, or together a CH2 group, and G is an oxygen atom or CH2, D-E is a group H2C-CH2, HC=CH, OC, CH(OH)-CH(OH), CH(OH)-CH2, O t \ 5 CH2-CH(OH), HC~CH , 0-CH2, or, if G represents a CH2 group, D-E is also CH2-O, W is a group C(=X)R.8, or a bicyclic or tricyclic aromatic or heteroaromatic radical, L3 is hydrogen, or, if a radical in W contains a hydroxyl group, forms a ] 0 group 0-L.4 with the latter, or, if a radical in W contains an amino group, forms a group NR^-L.4 with the latter, R25 is hydrogen or Cj-Ciq alkyl, X is an oxygen atom, or two OR^O groups, or a C2-C10 alkylenedioxy group that may be straight or branched, or H/OR^, or a CR^R* 1 group, 15 r8 is hydrogen, C1 -C j 0 alkyl, aryl, aralkyl, halogen or CN, and is hydrogen or a protective group PG^, RlO.Rll , in each case independently of one another, are hydrogen, Ci -C20 alkyl, aryl, aralkyl, or together with a methylene carbon atom form a 5-to 7-membered carbocyclic ring, 20 Z can represent oxygen or H/OR12, Rl2 can represent hydrogen or a protective group PG^, AMENDED SHEET WO 2004/012735 PCT/EP2003/008483 115 A-Y can represent a group 0-C(=0), O-CH2, CH2~C(=0), NR21 -C(=0) or NR21-S02, r20 can represent C1-C20 alkyl, R21 can represent a hydrogen atom or Cj-Cjo alkyl, 5 PG^, PGY, and PG^ can represent a protective group PG, and L,l, L2, and iA independently of one another, can represent hydrogen, a group C(=0)C1, a group C(=S)C1, a group PG^ or a linker of general formula (III) or (IV); provided that at least one substituent L1, L2 or L4 represents a linker of 10 general formula (III) or (TV); the linker of general formula (III) has the following structure, T 20 A HI >^u—(ay—•v—(CH2)—FG' in which T can represent oxygen or sulfur, 15 U can represent oxygen, CHR22, CHR22-NR23-C(=0)-, 0-C(=0)-CHR22-NR23-C(=0>, 0-C(=0)-CHR22-NR23-C(=S)-, CHR22-NR23-C(=S)- orNR24a, 0 can represent 0 to 15, V can represent a bond, aryl, a group NR24b-C(-0)-0-(CH2)s ^ u * or a group WO 2004/012735 PCT/EP2003/008483 116 NR24b-C(=S)-0-(CH2)s— Q— 9 s can represent 0 to 4, Q can represent a bond, 0-C(=0)-NR24c} 0-C(=S)-NR24c, 15 -0-C(=0)-NR24c—<T^ -0-C(=S)-NR24c—^ 5 , or R22 can represent hydrogen, Cj-Cjo alkyl, aryl or aralkyl, r23 can represent hydrogen or C^-Cjo alkyl, R24a} R24b9 and r24c; independently of one another, can represent hydrogen or Cj-Cio alkyl, 10 q can represent 0 to 15, o. -» N o Xf Xf FG1 can represent C j -C i q alkyl-S3 , ° , Br CI O -[kJ -S-II ° , or CO2H; and the linker of general formula (IV) has the following structure, T w— IV, (CH2).-W?-C(=0)-U— (CH2)—FG1 in which T can represent oxygen or sulfur, W1, W2 are the same or different and can represent oxygen or NR24® o can represent 0 to 5, PCT/EP2003/008483 117 can represent hydrogen or C1-C10 alkyl, can represent halogen, CN, NO2, CO2R28, or OR28, can represent hydrogen, C1-C10 alkyl, aryl or aralkyl, can represent 0 to 5, can represent oxygen, CHR22, CHR22-NR23-C(=0)-, CHR22-NR23-C(=S)- or C,-C20 alkyl, can represent hydrogen, Cj-Ciq alkyl, aryl or aralkyl, can represent hydrogen or Cj-Cio alkyl, can represent 0 to 20, can represent C1-C10 alkyl-S3, o -•Go Xf Xf JU S , B, _ a , 8 ,orCO2H, as a single isomer or a mixture of different isomers and/or as a phannaceutically acceptable salt thereof. 15

2. Effector conjugate according to claim 1, wherein: A-Y represents 0-C(=0) or NR21 -C(=0), D-E represents an H2C-CH2 group, G represents a CH2 group, Z represents an oxygen atom, 20 Rla, R^5 in each case represent Cj-Cio alkyl or together a -(CH2)p group with p equal to 2 or 3 or 4, R2a R2b3 independently of one another, represent hydrogen, Ci-Cjo alkyl, C2-C10 alkenyl, or C2-C10 alkynyl, WO 2004/012735 24a R R27 R28 q 5 u R22 R23 r 10 FG1 WO 2004/012735 PCT/EP2003/008483 118 R.3 represents hydrogen, R4a, g4b independently of one another, represent hydrogen orC^-Cjo alkyl; R.5 represents hydrogen, or C1-C4 alkyl or CH2OH or CH2NH2 or CH2N(alkyl, acyl) 12 or CH^Hal, 5 and R? together represent an additional bond or together an NH group, or together an N-alkyl group, or together a CH2 group, or together an oxygen atom, W represents a group C(=X)R8 or a 2-methylbenzothiazol-5-yl radical or a 2-methylbenzoxazol-5-yl radical or a quinolin-7-yl radical or a 10 2-aminomethylbenzothiazol-5-yl radical or a 2-hydroxymethylbenzothiazol-5-yl radical or a 2-aminomethyl-benzoxazol-5-yl radical or a 2-hydroxymethylbenzoxazol-5-yl radical, X represents a CR* ^r! 1 group, r8 represents hydrogen or C \ -C4 alkyl or a fluorine atom or a chlorine 15 atom or a bromine atom, r10/r1 1 represent hydrogen/2-methylthiazol-4-yl or hydrogen/2-pyridyl or hydrogen/2-methyloxazol-4-yl or hydrogen/2-anodnomethylthiazol-4-yl or hydrogen/2-aminomethyloxazol-4-yl or hydrogen/2-hydroxymethylthiazol-4-yl or hydrogen/2-hydroxymethyloxazol-4-yl. 20

3. Effector conjugate according to claim 1 or 2, wherein the effector element is selected from the group that consists of: (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; * WO 2004/012735 PCT/EP2003/008483 119 (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-thiazol-4-yl)-l-methyl-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(E))-16-[2-(2-Aminomethyl-thiazol-4-yI)-1 -methyl-vinylJ-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (1 S,3S(E),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-8,8,10,12,16-pentamethyl-3-[1 -methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-l-methyl-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione; (1 S,3 S(E),7S, 10R,11S,12S,16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-1 -methyl-vinyl]-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S, 13Z, 16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-thiazol-4-yl)-l-methyl-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(E))-16-[2-(2-Aminomethyl-thiazol-4-yl)-1 -methyl-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (1S,3S(E),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3 S(E),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-l -methyl-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyciofl 4.1.0]hepta-decane-5,9-dione; WO 2004/012735 PCT/EP2003/008483 120 (1 S,3 S(E),7S,10R,11 S,12S, 16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-1 -methyl-vinyl]-7,11-dihydroxy-l 0-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione; (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-5 fluoro-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-thiazol-4-yl)-l-fluoro-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(Z))-16-[2-(2-Aminomethyl-thiazol-4-yl)-1 -fluoro-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; 10 (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3- [l-fluoro-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9 dione; (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-1 -fluoro-vinyl] -8,8,10,12,16-pentamethyl-4,17-dioxa-15 bicyclo[14.1.0]heptadecane-5,9-dione; (lS,3S(Z),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l-fluoro-vinyl3-7,ll-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[l-20 chloro-2-(2-methyl-thiazol-4-yl)-vinyl] -oxacyclohexadec-13 -ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-thiazol-4-yl)-l -chloro-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-l 3-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-chloro-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 121 (lS,3S(Z),7S,10R,nS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-chloro-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-5 thiazol-4-yl)-l-chloro-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (lS,3S(Z),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l-chloro-vinyl]-7,l 1 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; 10 (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l- fluoro-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z,16S(Z))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-thiazol-4-yl)-l-fluoro-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-fluoro-15 vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (1S,3S(Z),7S,10R,1 lS,12S,16R)-7,ll-Dihydroxy-10-ethyl-8,8J12,16-tetramethyl-3-[l-fluoro-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[l 4.1,0]heptadecane-5,9-dione; (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3 -[2-(2-hydroxymethyl-20 thiazol-4-yl)-1 -fluoro-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione; (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-3 -[2-(2-Aminomethyl-thiazol-4-yl)-1 -fluoro-vinyl] -7,11 -dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1,0]hepta-decane-5,9-dione'; WO 2004/012735 PCT/EP2003/008483 122 (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-chloro-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-thiazol-4-yl)-l-chloro-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; 5 (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-thiazol-4-yl)-l-chloro- vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (1S,3S(Z),7S,10R,11S,12S,16R)-7,11 -Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-chloro-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione; 10 (1S,3S(Z),7S,10R,11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl- thiazol-4-yl)-1 -chloro-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione; (lS,3S(Z),7S,10R,llS512S516R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-l-chloro-vinyl]-7,l 1 -dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-15 bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z, 16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[l-methyl-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (IS,3S(E),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-methyl-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; 20 (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l- methyl-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (1S,3S(E),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-methyl-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; WO 2004/012735 PCT/EP2003/008483 123 (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-5,5?7,9,l 3-pentamethyl-l 6-[l -fluoro-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13 -ene-2,6-dione; (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-fluoro-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-chloro-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[l-chloro-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-fluoro-2-(2-pyridyl)-vinyl3-oxacyclohexadec-13-ene-2,6-dione; (1 S,3S(Z),7S, 10R,11S, 12S, 16R)-7,11 -Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-fluoro-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z, 16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-[l -chIoro-2-(2-pyridyl)-vinyl]-oxacyclohexadec-13 -ene-2,6-dione; (lS,3S(Z),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-chloro-2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S, 13Z, 16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[l -methyl-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13 -ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-yl)-l-methyl-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(E))-16-[2-(2-Aminomethyl-oxazol-4-yl)-1 -methyl-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 124 (lS,3S(E),7S,10R,llS,12S,16R)-7,n-Dihydroxy-8,8,10,12,16-pentamethyl-3-[1 -methyl-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-l -methyl-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3S(E),7S, 10R,11S, 12S, 16R)-3 - [2-(2-Aminomethyl-oxazol-4-yl)-1 -methyl-vijayl]-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S, 13Z, 16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-[l -methyl-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z,16S(E))-4,8-Dihydroxy-l 6-[2-(2-hydroxymethyl-oxazol-4-yl)-l-methyl-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R58S,9S,13Z,16S(E))-16-[2-(2-Aminomethyi-oxazol-4-yi)-l-methyl-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (1S,3S(E),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[ 1 -methyl-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-l -methyl-vinyl]-l O-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione; (lS,3S(E),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-l-methyl-vinyl]-7,ll-dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1.0]hepta-decane-5,9-dione; WO 2004/012735 PCT/EP2003/008483 125 (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l-fluoro-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8 S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-yl)-l-fluoro-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; 5 (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-oxazol-4-yl)-l-fiuoro- vinyl3-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-8,8,10,12,16-pentamethyl-3 -[l-fluoro-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; 10 (1S,3S(Z),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-[2-(2-hydroxymethyl- oxazol-4-yl)-l-fluoro-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-1 -fluoro-vinyl]-7,ll-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa- 15 bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[l -chloro-2-(2-methyl-oxazol-4-yl)-vmyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-yl)-l-chloro-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; 20 (4S,7R,8S,9S, 13Z, 16S(Z))-16-[2-(2-Aminomethyl-oxazol-4-yl)-l -chloro- vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (1 S,3S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-8,8,10,12,16-pentamethyl-3 -[l-chloro-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9- WO 2004/012735 PCT/EP2003/008483 126 (1 S,3S(Z),7S,1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-1 -chloro-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.L0]heptadecane-5,9-dione; (1 S,3S(Z),7S, 1 OR, 11S, 12S, 16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-1 -chloro-> vinyl]-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[l-fluoro-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-) yl)-l-fluoro-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S(Z))-16-[2-(2-Aminoraethyl-oxazol-4-yl)-1 -fluoro-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (1S,3S(Z),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-fluoro-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-5 bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-oxazol-4-yl)-l -fluoro-vinyl]-1 O-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione; (lS,3S(Z),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-l-fluoro-0 vinyl]-7,11 -dihydroxy-1 O-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1,0]hepta-decane-5,9-dione; (4S,7R,8S,9S, 13Z, 16S(Z))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-[ 1 -chloro-2-(2-methyl-oxazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(Z))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-oxazol-4-5 yl)-l -chloro-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-l 3-ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 127 (4S,7R,8S,9S,13Z,16S(Z))-16-[2-(2-Aminomethyl-oxazol-4-yl)-l -chloro-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (lS,3S(Z),7S,10R,llS,12S,16R)-7,n-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[l-chloro-2-(2-methyl-oxazol-4-yl)-vinyl]-4,17-dioxa-5 bicyclo[14.1.0]heptadecane-5,9-dione; (1S ,3 S(Z),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3 -[2-(2-hydroxymethyl-oxazol-4-yl)-1 -chloro-vinyl]-1 O-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione; (lS,3S(Z),7S,10R,llS,12S,16R)-3-[2-(2-Aminomethyl-oxazol-4-yl)-l-chloro-10 vinyl]-7,l l-dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]hepta-decane-5,9-dione; (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-thiazol-4-15 yl)-vinyl]-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(E))-16-[2-(2-Aminomethyl-thiazol-4-yl)-vinyl]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (1 S,3 S(E),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-8,8,10,12,16-pentamethyl-3 -[2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; 20 (1 S,3S(E),7S, 1 OR, 11S, 12S, 16R)-7,11-Dihydroxy-3-[2-(2-hydroxymethyl- thiazol-4-yl)-vinyl]-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3S(E),7S, 10R,11S, 12S, 16R)-3-[2-(2-Aminomethyl-thiazol-4-yl)-vinyl]-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-25 dione; WO 2004/012735 PCT/EP2003/008483 128 (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-[2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z, 16S(E))-4,8-Dihydroxy-16-[2-(2-hydroxymethyl-thiazol-4-yl)-vinyl]-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S(E))-16-[2-(2-Aminomethyl-thiazol-4-yl)-vinyl]-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (1 S,3 S(E),7S, 10R, 11S, 12S, 16R)-7,11 -Dihydroxy-1 O-ethyl-8,8,12,16-tetramethyl-3-[2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3 S(E),7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-[2-(2-hydroxymethyl-thiazol-4-yl)-vinyl]-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5,9-dione; (1 S,3S(E),7S, 1 OR, 11S, 12S,16R)-3-[2-(2-Aniinomethyl-thiazol-4-yl)-vinyl]-7,11-dihydroxy-1 O-ethyl-8,8,12,16-tetramethyl-4,l 7-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-l 6-[2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (lS,3S(E),7S,10R,llS,12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-[2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z, 16S(E))-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-[2-(2-pyridyl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione; (1S,3S(E),7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-[2-(2-pyridyl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 129 (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z, 16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (1S,3S,7S, 10R, 11S, 12S,16R)-7,ll-Dihydroxy-8,8,10,12,16-pentamethyl-3-(2-methyl-benzothiazol-5-yl)-4,l 7-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo [14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,1 lS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,l 1-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5- t yl)-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzothiazol-5 -yl)-4,8-dihydroxy-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3S,7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; WO 2004/012735 PCT/EP2003/008483 130 (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,ll-dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S, 13Z,16S)-4,8-Dihydroxy-7-propyl-5,5,9,13-tetramethyl-16-(2-5 methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-7-propyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-propyl-5,5,9,13-tetramethyl-oxacyclohexadec-l 3-ene-2,6-dione; 10 (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-propyl-8,8,12,16- tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[ 14.1,0]heptadecane-5,9-dione; (1 S,3S,7S,1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-propyl-8,8,12,16-tetramethyl-4,17-dioxa-15 bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3S,7S,1 OR, 11S, 12S, 16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,11-dihydroxy-10-propyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[l 4.1 .Ojheptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-butyl-5,5,9,13-tetramethyl-16-(2-20 methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-7-butyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-butyl-5,5,9,13-tetramethyl-oxacyclohexadec-l 3-ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 131 (1 S,3S,7S.10R.1 IS, 12S,16R)-7,1 l-Dihydroxy-10-butyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3 S,7S, 10R,11 S,12S,16R)-7,11 -Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-butyl-8,8,12,16-tetramethyl-4,17-dioxa-5 bicyclo [14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,1 lS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,l 1-dihydroxy-10-butyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S, 13Z,.l 6S)-4,8-Dihydroxy-7-allyl-5,5,9,13-tetramethyl-16-(2-10 methyl-benzothiazol-5-yl)-oxacyclohexadec-l 3-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-7-allyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-allyl-5,5,9,13-tetramethyl-oxacyclohexadec-13 -ene-2,6-dione; 15 (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-allyl-8,8,12,16-tetramethyl- 3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3S,7S,10R,11 S,12S,16R)-7,11 -Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-l 0-allyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione; 20 (1S,3S,7S,10R,11S, 12S, 16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,11- dihydroxy-10-allyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-prop-2-inyl-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-l 3 -ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 132 (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzothiazol-5-yl)-7-prop-2-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-458-dihydroxy-7-prop-2-inyl-5,5,9,13 -tetramethyl-oxacyclohexadec-13-ene-2,6-dione; 5 (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-prop-2-inyl-8,8,12,16- tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-prop-2-inyl-8,8,12,16-tetramethyl-4,17-dioxa-10 bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,11-dihydroxy-10-prop-2-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-but-3-enyl-5,5,9,13-tetramethyl-16-15 (2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13 -ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-l 6-(2-hydroxymethyl-benzothiazol-5-yl)-7-but-3-enyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-but-3-enyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; 20 (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-but-3-enyl-8,8,12,16- tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-but-3-enyl-8,8,12,16-tetramethyl-4,17-dioxa-25 bicyclo[l 4.1,0]heptadecane-5,9-dione; WO 2004/012735 PCT/EP2003/008483 133 (1 S,3 S,7S, 1 OR, 11S, 12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,11-dihydroxy-10-but-3-enyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1,0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S>4,8-Dihydroxy-7-but-3-inyl-5,5,9,13-tetramethyl-16-(2-methyl-benzothiazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z,16S)-4,8-Dihydroxy-l 6-(2-hydroxymethyl-benzothiazol-5-yl)-7-but-3-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzothiazol-5-yl)-4,8-dihydroxy-7-but-3-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13 -ene-2,6-dione; (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-but-3-inyl-8,8,12,16-tetramethyl-3-(2-methyl-benzothiazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-3-(2-hydroxymethyl-benzothiazol-5-yl)-10-but-3 -inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzothiazol-5-yl)-7,ll-dihydroxy-10-but-3 -inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-5,5,7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-oxacyclohexadec-l 3-ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 134 (lS3SJS,10R,llSJ2S46R>7,ll-Dihydroxy-8,8,10,12>16-penlairieaiyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[l 4.1.0]heptadecane-5 5,9-dione; (1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,11 -dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S, 13Z,16S)-4,8-Dihydroxy-7-ethyl-5,5,9,13-tetramethyl-l 6-(2-10 methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-ethyl-5,5,9,13 -tetramethyl-oxacyclohexadec-13 -ene-2,6-dione; 15 (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-10-ethyl-8,8,12,16-tetramethyl- 3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.03heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-10-ethyl-858,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; 20 (lS,3S,7S,10R,llS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,ll- dihydroxy-10-ethyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-7-propyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 135 (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-propyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-propyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; 5 (1S,3S,7S,10R,11S,12S,16R)-7,11 -Dihydroxy- 10-propyl-8,8,12,16- tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-l 0-propyl-8,8,12,16-tetramethyl-4,17-dioxa-10 bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,1 lS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,l 1-dihydroxy-10-propyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-butyl-5,5,9,13-tetramethyl-16-(2-15 methyl-benzoxazol-5-yl)-oxacyclohexadec-l 3-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-l 6-(2-hydroxymethyl-benzoxazol-5-yl)-7-butyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z, 16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-butyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; 20 (1S ,3 S,7S, 1 OR, 11S, 12S,16R)-7,11 -Dihydroxy-10-butyl-8,8,12,16-tetxamethyl- 3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-l 0-butyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; WO 2004/012735 PCT/EP2003/008483 136 (1 S,3S,7S, 10R,11S, 12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,l 1 -dihydroxy-10-butyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z, 16S)-4,8-Dihydroxy-7-allyl-5,5,9,13-tetramethyl-16-(2-5 methyl-benzoxazol-5-yl)-oxacyclohexadec-l 3-ene-2,6-dione; (4S,7R,8S,9S, 13Z, 16S)4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-allyl-5,5,9,13 -tetramethyl-oxacyclohexadec-13 -ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-allyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; 10 (1S,3S,7S510R,1 1S,12Ss16R)-7,1 l-Dihydroxy-10-allyl-8,8,12,l6-tetramethyl- 3-(2-methyl-benzoxazol-5-yl)4,17-dioxa-bicyclo[14.1.0]heptadecane-559-dione; (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-10-allyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; 15 (1S,3S,7S,10R,1 lS,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,l 1- dihydroxy-10-allyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-prop-2-inyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; 20 (4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5- yl)-7-prop-2-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-prop-2-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; WO 2004/012735 PCT/EP2003/008483 137 (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-10-prop-2-inyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-10-prop-2-inyI-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,11-dihydroxy-10-prop-2-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-but-3-enyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-l 6-(2-hydroxymethyl-benzoxazol-5-yl)-7-but-3 -enyl-5,5,9,13 -tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy-7-but-3-enyl-5,5,9,13 -tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-but-3-enyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,1 l-Dihydroxy-3-(2-hydroxymethyl-benzoxazol-5-yl)-10-but-3-enyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1,0]heptadecane-5,9-dione; (1 S,3 S,7S, 1 OR, 11S, 12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,11-dihydroxy-10-but-3-enyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione; WO 2004/012735 PCT/EP2003/008483 138 (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-7-but-3-inyl-5,5,9,13-tetramethyl-16-(2-methyl-benzoxazol-5-yl)-oxacyclohexadec-13 -ene-2,6-dione; (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-16-(2-hydroxymethyl-benzoxazol-5-yl)-7-but-3 -inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13 -ene-2,6-dione; 5 (4S,7R,8S,9S, 13Z, 16S)-16-(2-Aminomethyl-benzoxazol-5-yl)-4,8-dihydroxy- 7-but-3-inyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione; (1 S,3 S,7S, 1 OR, 11S, 12S, 16R)-7,11 -Dihydroxy-10-but-3-inyl-8,8,12,16-tetramethyl-3-(2-methyl-benzoxazol-5-yl)-4,l 7-dioxa-bicyclo[14.1 .Ojheptadecane-5,9-dione; 10 (lS,3S,7S,10R,llS,12S,16R)-7,ll-Dihydroxy-3-(2-hydroxymethyl- benzoxazol-5-yl)-10-but-3-inyl-8,8,12,16-tetramethyl-4,17-dioxa-bicyclo[ 14.1.0]heptadecane-5,9-dione; (1 S,3S,7S,10R, 11 S,12S,16R)-3-(2-Aminomethyl-benzoxazol-5-yl)-7,11-dihydroxy-10-but-3-inyl-8,8,12,l 6-tetramethyl-4,17-dioxa- 15 bicyclo[ 14.1,0]heptadecane-5,9-dione, wherein the hydrogen atoms in the above-mentioned effector elements are replaced in the positions indicated in formula (I) by radicals L'-L3.

4. Effector conjugate according to any one of claims 1-3, wherein the linker is 20 selected from the group that consists of the compounds of general formula (III), wherein V represents a bond or an aryl radical, o is zero, and T is an oxygen atom. 25 WO 2004/012735 PCT/EP2003/008483 139

5. Effector conjugate according to any one of claims 1-3, wherein the linker is selected from the group that consists of the compounds of general formula (III), wherein V represents a bond or an aryl radical or a group NR24b-C(=0)-0-(CH2)s— o is 0 to 4, and -0-C(=0)-NR24C— Q is a bond or a group

6. Effector conjugate according to claim 5, wherein 10 V is a bond or a group NR24b-C(=0)-0-(CH2)„—Q -0-C{=0)-NR240-^^ Q is a bond or a group o is 0,2 or 3, s is 1, and 15 T is an oxygen atom.

7. Effector conjugate according to any one of claims 1-3, wherein the linker is selected from the group that consists of compounds of general formula (IV), wherein o is 0 to 4, and 20 q is 0 to 3. WO 2004/012735 PCT/EP2003/008483 140

8. Effector conjugate according to claim 7, wherein 0 is 0,2 or 3, W1 is oxygen, q is 0, 5 R22 is hydrogen, C1-C3 alkyl or aralkyl, R23 is hydrogen or C1-C3 alkyl, R24a is hydrogen or C1-C3 alkyl, R27 is fluorine, chlorine, CN, NO2, CO2R28 or OR28, R28 is hydrogen or C1-C5 alkyl, and 10 U is oxygen, CHR22, or CHR22-NR23-C(=0)-.

9. Effector recognition unit conjugate of general formula (I), 15 wherein the substituents therein have the meanings that are mentioned in claim 1, but at least one group FG1 is replaced by a group FG2a or FG2b, wherein FG2a or FG2b can have the following meanings: WO 2004/012735 141 PCT/EP2003/008483 o o /. 2, » -i-^s FG2a: -S-S-, ° , Br 5 ci , o ; FG2b: -CONH-; and wherein a recognition unit is conjugated via a sulfur atom with the group FG or via an amide function with group FG2b; wherein the recognition unit is selected from 5 the group that consists of peptides, soluble receptors, cytokines, lymphokines, aptamers, spiegelmers, recombinant proteins, new framework structures, monoclonal antibodies and fragments of monoclonal antibodies; as a single isomer or a mixture of different isomers and/or as a phannaceutically acceptable salt thereof. 0

10. Effector recognition unit conjugate according to claim 9, wherein the conjugate contains more than one recognition unit, and wherein the recognition units are identical. 15

11. Effector recognition unit conjugate according to claim 9 or 10, wherein the recognition unit is an antibody, or an antigen-binding fragment thereof, which is specific for an antigen that is selected from the group that consists of the antigens that are cited in Table 1, as well as CD19, CD20, CD40, CD22, CD25, CD5, CD52, CD10, CD2, CD7, CD33, CD38, CD40, CD72, CD4, CD21, CD37, CD30, VCAM, CD31, 20 ELAM, endoglin, VEGFRI/II, avp3, Tiel/2, TES23 (CD44ex6), phosphatidylserine, PSMA, VEGFR/VEGF complex and ED-B-fibronectin. 142

12. Method for the production of effector conjugates according to any one of claims 1-8, wherein a compound of general formula (I), wherein the substituents have the meanings that are mentioned in claim 1, but the condition that at least one substituent L*, L2 or L4 represent a linker of general formula (III) or (IV) need not be met, and at least one substituent iJ, L2 or L4 represents hydrogen, a group C(=0)C1, or a group C(=S)C1, is reacted with a linker that is selected from the group that consists of: a linker of general formula (III1): RG1 (CH2)-V— (CH2)—FG1 |||i, in which RG1 is an 0=C=N group or an S=C=N group, and o, V, q and FG1 have the meanings that are mentioned in claim 1; or a linker of general formula (III): RG2 (CH2)-V—(CH2)—FG' III2, in which RG2 is a Hal-C(=T)-CHR22 group, or a Hal-C(=T>CHR22-NR23-C(=T) group, or an R26-C(=0)-0-C(=T)-CHR22 group, or an R26-C(=0)-0-C(=T)-CHR22-NR23-C(=T) group, wherein R2^ is Ci-Cjq alkyl, aryl, or aralkyl, and o, V, q and FG1 have the meanings that are mentioned in claim 1; or a linker of general formula (III): RG3 (CH2)—V—(CH2)—FG' |||3, in which RG3 is an OH group, or an NHR24a group, or a COOH group, and o, V, q and FG1 have the meanings that are mentioned in claim 1; Intellectual Property Office of N.2. 27 NOV 2006 RECEIVED 143 or a linker of general formula (IV1): RG'— (CH2)c—$ IV1 ■(CH2)„—vr-C(=0)—U-(CH2)—FG1 9 in which 5 RG1 is an 0=C=N group or an S=C=N group, and o, q, r, W2, R27, U and FG1 have the meanings that are mentioned in claim 1; r\ or a linker of general formula (IV ): R27 RG2— (CH2)„—<f 3 • IV2 \=^(CH2)q—W-C(=0)—U—(CH2)—FG1 j 10 in which rg2 is a Hal-c(=T)-CHR22 group, or a Hal-C(=T)-CHR22-NR23-C(=T) group, or an r26-C(=0)-0-C(=T)-CHR22 group, or an r26-c(=0)-0-c(=T)-chr22-NR23-c(=T) group, wherein is C^-Cjo alkyl, aryl, or aralkyl, and r22, r23, T, o, q, r, w2, r27, u and fg! have the meanings that are mentioned in claim 1; 15 or a linker of general formula (iv3): R 27 RG3—(CH2) // '•% 2>0 •(CHj)—'W^-C(=0)—U-(CH2)—FG1 IV3 in which Intellectual Property Office of N.Z. 27 NOV 2006 RECE I V E D 144 RG3 is an OH group or an NHR^4a group or a COOH group, and R24, o, q, r, W2, R27, U and FG1 have the meanings that are mentioned in claim 1.

13. A method according to claim 12, wherein in the linkers of general formulae (III1), (III2) and (III3), V represents a bond or an aryl radical, o is equal to zero, and T is an oxygen atom.

14. A method according to claim 12, wherein in the linkers of general formulae (III1), (III2) and (III3), V represents a bond or an aryl radical or a group o is 0 to 4, and Q is a bond or a group

15. A method according to claim 14, wherein V is a bond or a group Q is a bond or a group o is 0,2 or 3, s is 1, and T is an oxygen atom. Intellectual Property otfla/S A/ t I M * Office of N.2. 27 NOV 2006 145

16. A method according to claim 12, wherein in the linkers of general formulae (IV1), (IV2) and (IV3), o is 0 to 4, and q is 0 to 3.

17. A method according to claim 16, wherein 0 is 0,2 or 3, W1 is oxygen, q is 0, R22 is hydrogen, C1-C3 alkyl or aralkyl, R23 is hydrogen or C1-C3 alkyl, R24a is hydrogen or C1-C3 alkyl, R27 is fluorine, chlorine, CN, N02, CO2R28 or OR28, R28 is hydrogen, or C1-C5 alkyl, and U is oxygen, CHR22, or CHR22-NR23-C(=0)-. Intellectual Property Office of N.Z. 27 NOV 2006 RECEIVFn 146

18. Method for the production of effector recognition unit conjugates according to any one of claims 9 to 11, wherein an effector conjugate according to any one of claims 1-8 is reacted with at least one recognition unit as defined in any one of claims 9 to 11.

19. Use of a compound of general formula (I), wherein the substituents have the meanings that are mentioned in claim 1, but the condition that at least one substituent L*, or I/* represent a linker of general formula (HI) or (IV) need not be met, and at least one substituent L*, L2 or iA represents hydrogen, a group C(=0)C1, or a group C(=S)C1, for the production of an effector conjugate according to any one of claims 1 to 8.

20. Use of a compound of general formula (I) for the production of an effector recognition unit conjugate according to any one of claims 9 to 11.

21. Use of a linker of general formula (ffl1), (III2), (III3), (IV1), (TV2) or (TV3) for the production of an effector conjugate according to any one of claims 1 to 8.

22. Use of a linker of general formula (HI1), (IH2), (ffl3), (IV1), (IV2) or (IV3) for the production of an effector recognition unit conjugate according to any one of claims 9 to 11.

23. Use of a recognition unit, as defined in claim 9 or 11, for the production of an effector recognition unit conjugate according to any one of claims 9 to 11.

24. Effector recognition unit conjugate according to any one of claims 9 to 11 for use as a medicament. Intellectual Property Office of N.Z. 27 NOV 2006 |M .mm. 147

25. Effector recognition unit conjugate according to any one of claims 9 to 11 for use as a medicament for treating diseases that are associated with proliferative processes.

26. Effector recognition unit conjugate according to any one of claims 9 to 11 for use as a medicament for treating a disease that is selected from the group that consists of tumors, inflammatory diseases, neurodegenerative diseases, angiogenesis-associated diseases, multiple sclerosis, Alzheimer's disease, and rheumatoid arthritis.

27. Use of an effector recognition unit conjugate according to any one of claims 9 to 11 for the production of a medicament or a pharmaceutical composition.

28. Use of an effector recognition unit conjugate according to any one of claims 9 to 11 for the production of a medicament for treating diseases that are associated with proliferative processes.

29. Use of an effector recognition unit conjugate according to any one of claims 9 to 11 for the production of a medicament for treating a disease that is selected from the group that consists of tumors, inflammatory diseases, neurodegenerative diseases, angiogenesis-associated diseases, multiple sclerosis, Alzheimer's disease, and rheumatoid arthritis.

30. An effector conjugate according to claim 1, substantially as herein described or exemplified.

31. An effector recognition unit conjugate according to claim 9, substantially as herein described or exemplified.

32. A method according to claim 12, substantially as herein described or exemplified. I ! — I ,n%ctual Property J Office of N.Z. I 2 7 NOV 2006 148

33. A method according to claim 18, substantially as herein described or exemplified.

34. A use according to claim 19, substantially as herein described or exemplified.

35. A use according to claim 20, substantially as herein described or exemplified.

36. A use according to claim 21, substantially as herein described or exemplified.

37. A use according to claim 22, substantially as herein described or exemplified.

38. A use according to claim 23, substantially as herein described or exemplified.

39. A use according to claim 27, substantially as herein described or exemplified.

40. A use according to claim 28, substantially as herein described or exemplified.

41. A use according to claim 29, substantially as herein described or exemplified. END OF CLAIMS Intellectual Property Office of N.Z. 27 NOV 2006 RECEIVED </div>