DE2851953A1 - 4-N-Substd. spectinomycyl-amine derivs. - useful as broad-spectrum antibacterial agents - Google Patents

Abstract

Spectinomycylamines of formula (I) and their acid-addn. salts are new. In (I) R2 is H or Me, and R1 is (a) 1-18C alkyl; (b) benzyl opt. substd. by 1-3 Me gps., 1-3 Cl atoms, an acetylamino gp., 1-3 OH gps., a dimethylamino gp., 1-3 MeO gps. or a methylenedioxy gp.; (c) cyclohexyl; (d) CH2CH2COR3, where R3 is 1-8C alkyl; (e) CH2CH2CH(OH)R4 where R4 is 1-4C alkyl or phenyl; (f) CH2COR5 where R5 is Me, chlorophenyl, methoxyphenyl, fluoro-substd. biphenylyl, 3,5-dibromo-j-aminophenyl, EtOH, NHMe,NHCH2COOEt, i-PrNH2, piperidino, hexamethylenimino, benzylamino, N-methyl1-methyl-2-hydroxy-2-phenylethylamino, anilino, N-methylanilino or methyl-, ethoxy-, phenoxy-, ethoxycarbonyl-, methoxy-carbonyl- or 3-acetyl-4-(2-methoxyethoxy)-anilino; (g) COR6, where R6 is 1-17C alkyl, phenyl benzyl, (CH2)nR7, CHOH(CH2)mNH2, CH(NH2)R8, (CH2)pNR9R10, 1-hydroxy-2-(ethylaminocarbonylamino)ethyl, (CH2)qCOR11, p-R12 NHCO-phenyl, (CH2)4CONHSp or (CH2)3NHCO(CH2)2CONHSp R7 is NH2, NHMe2, pyroolidino, 4-benzylpiperidino, morpholino or N-methylpiperazino and n = 1-4. m = 1 or 2; R8 is Me, CH2OH, Pr, benzyl or 4-amino-3,5-dichlorophenyl; R9 is H or Me, R10 is acetyl, dodecyl or benzoyl and p = 1-4; R11 is phenyl, 2-18C alkylamino, di(1-12C alkyl)amino, anilino, benzylamino, dibenzylamino, pyroolidino, 4-benzylpiperidino, morpholino, thiomorpholino, N-methylpiperazino or aminocarbonylmethylamino, and q = 2-4; R12 is hexyl or dodecyl; and Sp is 4-spectinomycyl. Cpds. (I) are broad-spectrum antimicrobial (esp. antibacterial) agents with high activity against Gram-positive and -negative bacteria and low toxicity (LD50 >2 g/kg, p.o.). Specified cpds. have higher activity than spectinomycin against E. coli in vivo.

Description

New Spectinomycylamines, Process for Their Manufacture

and medicaments containing them The invention relates to new spectinomycylamines of the general formula I, their physiologically compatible acid addition salts with inorganic or organic acids, processes for their production and pharmaceuticals containing these substances.

The 4 (R) -Spectinomycylamines of the general formula I can also be used as Decahydro-4a, 7,9-trihydroxy-4-subs.amino-2-methyl-6,8-bis (methylamino) -pyrano [2,3-b] [1,4] benzodioxins to be discribed. These compounds and their physiologically acceptable salts have an excellent antimicrobial effectiveness with good tolerance and are thus the well-known Spectinomycin (formerly also known as Actinospectacin) significantly superior to broad spectrum antibiotics.

In the above general formula I: R1 is a straight-chain or branched alkyl group with 1 to 18 carbon atoms, the benzyl group, the mono-, di- or tri-methylbenzyl group, the mono-, di- or trichlorobenzyl group, an acetylaminobenzyl group, the mono-, Di- or tri-hydroxybenzyl group, a dimethylaminobenzyl group, the mono-, di- or tri-methoxybenzyl group, the methylenedioxybenzyl group, the cyclohexyl group; a group of the general formula II, in which R3 represents a straight-chain or branched alkyl group having 1 to 8 carbon atoms; a group of the general formula III, in which R4 represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms or the phenyl group; a group of the general formula IV, in which R5 is the methyl group, a chlorophenyl group, a methoxyphenyl group, a fluorine-substituted biphenyl group, the 3,5-dibromo-4-aminophenyl group, the xthoxy group, the methylamino, ethoxycarbonylmethylamino or isopropylamino group, the piperidino or hexamethyleneamino group, the the N-methyl- (1-methyl-2-hydroxy-2-phenyl) ethylamino group, the anilino, N-methylanilino, a methylanilino, an ethoxyanilino, phenoxyanilino, ethoxycarbonylanilino, methoxycarbonylanilino or the 3- Represents acetyl 4- (2-methoxy) ethoxyanilino group; or a group of the general formula V, in which R6 is a straight or branched alkyl group with 1 to 17 carbon atoms, the phenyl or benzyl group or a group of the general formula VI, - (CH2) n-R7 (VI) in which R7 is the free amino group, the methyl or dimethylamino group , represents the pyrrolidino, 4-benzylpiperidino, morpholino or N-methylpiperazino group and n has the numbers 1 to 4, R6 can also be a group of the general formula VII, in which m stands for the numbers 1 or 2, furthermore a group of the general formula VIII, in which R8 denotes the methyl, hydroxymethyl, propyl, benzyl or 4-amino-3,5-dichlorophenyl group, or a group of the general formula IX, in which Rg represents a hydrogen atom or the methyl group, R10 represents the acetyl, dodecyl or benzoyl group and p represents an integer from 1 to 4, but R6 can also represent the 1-hydroxy-2- (ethylaminocarbonyl) aminoethyl radical or a group of the general Formula X, (CH2) 'CO'R11 (X) in which q the numbers 2, 3 or 4 and R11 the phenyl group, a straight-chain or branched alkylamino group with 2 to 18 carbon atoms, a dialkylamino group whose alkyl radicals contain 1 to 12 carbon atoms, the anilino group, the benzylamino group, the dibenzylamino group, the pyrrolidino group, the 4-benzylpiperidino group, the morpholino, thiomorpholino, N-methylpiperazino or aminocarbonyl-methylamino group, furthermore R6 can mean a group of the general formula XI, in which R12 denotes the hexyl or dodecyl radical, but finally R6 can also represent the groups of the general formulas XII and XIII have as their subject, where in these formulas Sp denotes the spectinomycyl (4>radical; and R2 denotes a hydrogen atom or the methyl group.

The 4-spectinomycylamines of the general formula I are prepared as described below: From a 4-spectinomycylamine derivative of the general formula XIV the residues Z are split off. In the general formula XIV, the radicals R1 and R2 have the meanings given above, and Z denotes a protective group known from peptide chemistry and easily cleavable by acidolytic cleavage or catalytic hydrogenation, such as the benzyloxycarbonyl group, the 4-erom or 4-nitro or 4-chloro-benzyloxycarbonyl group, the 4-methoxy or 3,4-dimethoxy or 3,4-methylenedioxy or 3,4, 5-trimethoxy or 4-decyloxy or 4-acetoxy or 4-ethoxy carbonyloxy-benzyloxycarbonyl group, a saturated or unsaturated alkoxycarbonyl group with 1 to 12 carbon atoms, optionally replaced by a furyl (2) group, a p-tolylsulfonyl group, one or more halogen atoms, an alkoxy or alkoxyalkoxy group with 1 to 3 carbon atoms may be substituted in the alkyl part and 1 to 3 carbon atoms in the alkylene part, for example furyl (2) methoxycarbonyl, allyloxycarbonyl, 2- (p-tolylsulfonyl) ethoxycarbonyl, 2-bromoethoxycarbonyl, 2,2,2-trichloro -ethoxycarbonyl-, 2- (2-tlethoxy-ethoxy) ethoxyearbonyl-, 3-methylpentyl- (3) -oxycarbonyl-but especially the tert-butyloxycarbonyl group, a cycloalkyloxycarbonyl group with 5 to 12 carbon atoms, like the cyclopentyloxycarbonyl or cyclohexyloxycarbonyl group, both of which are methyl -, ethyl or tert-butyl group, the isobornyloxycarbonyl or the adamantyl (1) oxycarbonyl group, a phenyl or biphenylalkoxycarbonyl group which can be substituted in the phenyl radical by one to three methyl or methoxy groups and their alkylene group, which can be straight or branched, contains 2 to 4 carbon atoms, such as, for example, dieot '«- dimethyl-3, 5-dimethoxy-benzyloxycarbonyl or 2- / biphenylyl- (41 / -propyl- (2) -oxycarbonyl group, the diphenyl methoxycarbonyl group, a phenyloxycarbonyl group which can optionally be substituted by a nitro, methoxy or methyl group, a dialkylaminooxycarbonyl group, such as the dimethylaminooxycarbonyl group or the P iperidinooxycarbonyl group, an alkylthiocarbonyl group with 1 to 4 carbon atoms in the alkyl radical, the benzylthiocarbonyl group, the formyl group or another aliphatic acyl group with 1 to 10 carbon atoms, which can optionally be substituted by 1 to 3 halogen atoms, hydroxyl groups, acyl radicals, or by a nitro group, such as the trifluoroacetyl, acetoacetyl, 2-nitrophenoxy-acetyl, monochloroacetyl, 3-chloro-butyroyl, 3-hydroxyisocaproyl group, furthermore Z can be a benzoyl, 2-nitrobenzoyl, 4-toluenesulfonyl, benzylsulfonyl or p- Methoxybenzenesulfonyl group or a benzyl or trityl group.

The residue Z is split off, for example, by means of a catalytic converter Hydrogenolysis in aqueous-organic or purely organic solvents such as alcohols, Acetic acid, dimethylformamide in the presence of noble metal catalysts such as palladium black, Palladium carbon or palladium on barium sulfate, platinum on carbon or by a acidolytic cleavage with a hydrohalic acid such as hydrogen chloride, Hydrogen bromide, with trifluoroacetic acid or an organic sulfonic acid in solvents like glacial acetic acid, chloroform, or dioxane. The optionally substituted phenyloxycarbonyl groups or benzyloxycarbonyl and dialkylaminooxycarbonyl groups pass through remove catalytic hydrogenation. The 2,2,2-trichloroethoxycarbonyl group is advantageously by the action of zinc powder in acetic acid or zinc dust removed in methanol. The benzyl group, on the other hand, is preferred by catalytic Hydrogenation in the presence of palladium, the trityl group by means of acidic saponification Acetic acid removed. Most of the groups Z can be, for example, with hydrogen bromide split off in glacial acetic acid at temperatures between 20 and 50 ° C.

Of particular importance are the benzyloxycarbonyl and 4-methoxy-benzyloxycarbonyl groups, which are produced by catalytic hydrogenation or by acidolytic cleavage with hydrogen chloride, Trifluoroacetic acid or boric acid tris-trifluoroacetate can be removed particularly easily permit.

The 4-specintomyclamines of the formula I can, if desired, then by means of inorganic or organic acids according to known methods in their physiological compatible acid addition salts are converted. The acids come, for example in question: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, maleic acid, Citric acid, tartaric acid, or fumaric acid.

The starting compounds of the general formula XIV can be prepared in various ways, depending on the meanings of the radicals R1 and R2. In general, spectinomycin is used, which is protected by introducing a protective group Z on the secondary amino groups in the 6- and 8-positions before the reaction. The basic radical is then introduced in the 4-position or, if a spectinomycylamine protected in the 6- and 8-position is present, the 4-amino group is alkylated or acylated. To prepare the starting substances of the general formula XIV, for example, the following processes are used: 1) Compounds of the general formula XIV, in which R1 is a straight-chain or branched alkyl group with 1 to 18 carbon atoms, the benzyl group, the mono-, di- or trimethylbenzyl group, the mono-, di- or tri-chlorobenzyl group, an acetylaminobenzyl group, the mono-, di- or trihydroxybenzyl group, a dimethylaminobenzyl group, the mono-, di- or trimethoxybenzyl group or the methylenedioxybenzyl group or the cyclohexyl group can be obtained by reacting a spectinomycin of the general Formula XV with a salt of the general formula XVI i1 3 3) A (-)) (XVI) in the presence of metal borohydrides.

In the above general formulas XV and XVI: R1 'denotes a straight-chain or branched alkyl group with 1 to 18 carbon atoms, the cyclohexyl group, the benzyl group, the mono-, di- or tri-methylbenzyl group, the mono-, di- or Tri-chlorobenzyl group, an acetylaninobenzyl group, the mono-, di- or tri-hydroxybenzyl group, a dimethylaminobenzyl group, the mono-, di- or trimethoxybenzyl group or the methylenedioxybenzyl group, and a halide anion, the sulfate, bisulfate, a Phosphate or nitrate anion; As already indicated above, Z is defined.

If, on the other hand, a compound of the general formula XIV is to be obtained in which R2 is the methyl group, the compound of the general formula XV is set with a salt of the general formula XVIa [R1 '- NH2 - CH3] (+) A (-) (XVIa) in the same way around.

Both reactions are carried out in water or in organic solvents, preferably in alcohols or in mixtures of the specified solvents Temperatures between 00 and 100 ° C., preferably between 00 and -500 ° C., carried out. Particularly suitable metal borohydrides are the alkali metal cyanoborohydrides, for example lithium cyanoborohydride, sodium cyanoborohydride or potassium cyanoborohydride.

2) The compounds of the general formula XIV in which the radical R1 has the meanings given above for the radical R1 'can also be obtained by reducing a spectinomycylamine derivative of the general formula XVII produce.

In the general formula XVII, Z is a, as defined in more detail above, by treatment with acids, bases or groups which can be easily split off by reduction and R13 represents a hydrogen atom or a straight-chain or branched alkyl group with 1 to 17 carbon atoms, the phenyl group, a mono-, di- or tri-methylphenyl group, a mono-, di- or tri-chlorophenyl group, an acetylaminophenyl group, a mono-, Di- or tri-hydroxyphenyl group, a dimethylaminophenyl group, a mono-, di- or tri-methoxyphenyl group, a methylenedioxyphenyl group or the cyclohexyl group.

Metal hydrides are used as reducing agents; it will be preferable Alkali borohydrides, for example sodium borohydride, are used. The reduction takes place in polar organic solvents, preferably in acetic acid or trifluoroacetic acid, at temperatures between 0 and 1500C.

3) To prepare a starting compound of the general formula XIV as described above, a spectinomycylamine of the general formula XVIII, in which Z is defined as described above, with an aldehyde of the general formula XIX, R13-CH = o (XIX) in which R13 has the meanings mentioned above (cf.

Formula XVII), in the presence of a reducing agent such as hydrogen or metal borohydrides, in a manner known per se to the starting product of the general Formula XIV to be implemented.

4) The starting compounds of the general formula XIV in which R1 the methyl or ethyl group and R2 denotes the methyl group, can also obtained by a compound of the general formula XIV in which R2 Is hydrogen and R1 is as defined above, with formaldehyde under reducing Implements conditions. The reaction takes place in the presence of metal borohydrides.

5) The starting compounds of the general formula XIV, in which R1 represents a group of the general formula II with the meanings given above for R3, can be represented by adding spectinomycylamines of the general formula XVIII anor, ß-unsaturated ketones of the general formula XX, in which R3 is defined as above. The addition takes place in solvents, for example alcohols, acetonitrile, dimethylformamide, dimethyl sulfoxide.

6) The starting compounds of the general formula XIV, in which R1 denotes a group of the general formula III, can be obtained, for example, by reducing spectinomycylamine derivatives of the general formula XXI, in which Z and R4 are as defined above. The reduction is achieved using hydrogen or a metal borohydride.

7) The starting compounds of the general formula XIV, in which R1 represents a group of the general formula IV, can be prepared by reacting a spectinomocyclamine of the general formula XVIII with an alkylating agent of the general formula XXII, in which Hal represents a halogen atom and R5 is as defined above. The reaction is carried out in solvents such as alcohols, dioxane, dimethylformamide, dimethyl sulfoxide or acetonitrile in the presence of a basic agent, preferably alkali metal carbonates, or hydrogen carbonates.

8) The starting compounds of the general formula XIV in which R1 a group of the general formula V with all of the meanings given there for R6 with the exception of the meaning of a group of the formula XII or XIII, can can be obtained, for example, by using a spectinomycylamine of the general Formula XVI II with an acid of the general formula XXIII R6 - COOH (XXIII) or acylated a reactive derivative of such an acid, the radical R6 being the has the meanings mentioned at the beginning. All are suitable for the acylation known methods, for example the reaction with acid halides, acid anhydrides, with activated esters, mixed anhydrides or reactions in the presence of Condensing agents such as carbodiimides.

The general reaction scheme is, depending on the structure of the Remainder R6, to be modified. In the radical R6 is a primary or secondary amino group present, e.g.

in formulas VI to X, it is recommended that those in these Residual primary or secondary amino groups present before the reaction with a Compound of formula XVIII by the introduction of a group Z as defined above is to be protected, whereby after completion of the implementation, mostly in the course of the 'production of the compounds of general formula I, including this radical Z with the other radicals Z of the general formula II is split off.

9) The starting compounds of the general formula XIV, in which R1 is a group of the general formula V in which R6 is a group of the general formula XII or XIII, is advantageously obtained by either one mole of a dicarboxylic acid of the general formula XXIV HOOC- (cH2).-COOH (XXIV) or the general formula XXV or a reactive derivative of these acids is reacted with 2 moles of the spectinomycylamine of the general formula XVIII. Possible implementation options are the conditions described for compounds XXIII.

The spectinomycins of the general formula XV are known from the literature or can be represented based on methods known from the literature.

The compounds of the general formula XVII can be obtained by acylation easily prepared from compounds of general formula XVIII, for example by reaction with acids of the formula R13 COOH, or their reactive derivatives, such as esters, halides and anhydrides.

The compounds of the general formula XVIII are obtained starting of compounds of the general formula XV; such a spectinomycin derivative is reacted with an ammonium salt in the presence of alkali metal cyanoborohydrides. the Implementation is carried out in water or in organic solvents, preferably in alcohols, or in mixtures of these, at temperatures between 00 and 1000C, preferably 00 and 500C. An ammonium halide, for example, is used as the ammonium salt, sulfate, phosphate or nitrate into consideration; preferably as alkali metal cyanoborohydride the sodium cyanoborohydride.

The compounds of the general formula XXI are obtained by reaction of spectinomycylamines of the general formula XVIII with ketones of the general Formula XXVI H2C = CH - COR4 (XXVI), in which R4 is defined as mentioned above.

The compounds according to the invention have a low toxicity strong and broad antimicrobial effectiveness.

They are particularly effective against bacteria and bacteria-like microorganisms and are therefore suitable for prophylaxis and chemotherapy of local and systemic Infections in human and veterinary medicine caused by these pathogens will.

For example, local and X or systemic diseases treated and / or prevented by the following pathogens or by Mixtures of the following pathogens are caused: Micrococcaceae, such as staphylococci; Lactobacteriaceae such as streptococci; Neisseriaceae such as Neisseria; Corynebacteriaceae, such as corynebacteria; Enterobacteriaceae, such as Escherichiae bacteria of the Coli group, Klebsiella bacteria, e.g., K. pneumonia; Proteae bacteria of the Proteus group e.g. Proteus vulgaris; Salmonella bacteria, e.g., S. thyphimurium; Shigella bacteria, e.g., Shigella dysenteriae, Pseudomonas bacteria, e.g., Pseudomonas aeruginosa; Aeromonas bacteria, e.g. Aeromonas lique faciens.

Spirillaceae such as Vibrio bacteria e.g. Vibrio cholerae; Parvobaoteriaceae or Brucellaceae such as Pasteurella bacteria; Brucella bacteria, e.g. Brucella abortus; Haemophilus bacteria, e.g., Haemophilus influenzae; Bordetella bacteria, e.g., Bordetella pertussis; Moraxella bacteria, e.g., Moraxella lacunata; Bacteroidaceae, such as Bacteroides bacteria, Fusiform bacteria, e.g., Fusobacterium fusiforme; Sphaerophorus bacteria, e.g.

Sphaerophorus necrophorus; Bacillaceae, such as aerobic spore formers, e.g., Bacillus anthracis; anaerobic spore-forming chlostridia, e.g., Clostridium perfrinsens; Spirochaetaceae such as Borrelia bacteria; Treponema bacteria, e.g., Treponema pallidum; Leptospira bacteria, such as Leptospira interrogans.

The above list of pathogens is only exemplary and by no means to be understood as restrictive.

As diseases that are prevented by the active ingredients according to the invention, that can be improved and / or cured are, for example: diseases the respiratory tract and the pharynx; Otitis; Pharyngitis; Pneumonia; Peritonitis; Pyelonephritis; Cystitis; Endocarditis; System infections; Bronchitis; Arthritis; local infections.

The effectiveness of the spectinomycylamines according to the invention can be demonstrate by means of the following examinations: 1. In Vitro tests The method of the serial dilution test was used for the investigations applied in the microtiter system. The substances were tested for bacteriostasis in liquid medium.

The bacteriostatic effect was examined at the following concentrations: 80; 40; 20 ;, 10; 5; 2.5; 1.25; 0.6 and 0.3 jug / ml. A broth served as the nutrient medium from 5 g peptone, 3 g meat extract, made up with distilled water to a Volume of 1000 ml; pH 6.7. The age of the primary cultures was 24 hours. The setting of the germ suspension was carried out on the photometer (according to "Eppendorf'2) (test tube diameter 14 mm, filter 546 nm) based on the turbidity of a barium sulfate comparison suspension, which was created by a barium sulphate suspension caused by the addition 3.0 ml of 1% barium chloride solution in 97 ml of 1% sulfuric acid was formed. To the setting were Streptococcus Aronson in a ratio of 1: 150 and the rest Test germs further diluted with a saline solution in a ratio of 1: 1500.

16 mg of the respective substance were weighed into 10 ml volumetric flasks and filled up to the mark with the solvent.

The further dilution series was with distilled water or the respective solvent produced.

The wells of the microtiter plates were filled with 0.2 ml nutrient medium, 0.01 ml of the corresponding substance dilution and with a drop of germ suspension charged and incubated for 18 to 20 hours at 370C. A solvent control was made always carried.

The reading was taken macroscopically, with the respective Limit concentration (= lowest bacteriostatically effective concentration) determined became.

The test organisms used were: Staphylococcus aureus SG 511, Streptococcus Aronson, Escherichia Coli ATCC 9637 and 11 775, Pseudomonas aeruginosa Hamburgensis and ATCC 10145, Serratia marcescens ATCC 13 880, Klebsiella pneumoniae ATCC 10 031, Proteus mirabilis Hamburgensis and Proteus vulgaris.

The following table lists the minimum inhibitory concentrations (MIC) determined for typical representatives of the compounds according to the invention: 4-N-Ethyl-4 (R) -spectinomycylamine = A 4-N-isopropyl-4 (R) -spectinomycylamine = B 4- N-dodecyl-4 (R) -spectinomycylamine r C 4-N-octadecyl-4 (R) -spectinomycylamine = D 4-N- (3-oxo) butyl-4 (R) -spectinomycylamine = E 4-N- ( 4-methyl-3-oxo) pentyl-4 (R) -spectinomycylamine = F 4-N- (lauroyl) -4 (R) -spectinomycylamine = G 4-N- (palmitoyl) -4 (R) -spectinomycylamine = H 4-N- (4- [dodecylamino-carbonyl]) butyryl-4 (R) -spectinomycylamine = I 4-N- (4- [tetradecylamino-carbonyl]) butyryl-4 (R) -spectinomycylamine = K 4-N - (4- [Dodecylamino-carbonyl]) benzoyl-4 (R) -spectinomycylamine 4-N- (ß) Alanyl-4 (R) -spectinomycylamine = M 4-N- (4'-amino-2'-hydroxy) butyryl-4 (R) -spectinomycylamine = N 4-N - (# - Amino) butyryl-4 (R) -spectinomycylamine = O 4-N- (p-methoxy) phenacyl-4 (R) -spectinomycylamine = P 4- N- (p- [4-fluoro] phenyl) phenacyl-4 (R) -spectinomycylamine 4-N- (4-amino-3,5-dibromo) phenacyl-4 (R) -spect inomycylamin amine MIC (µg / ml) Verb. Staph. Strept. E. coli E. coli Pseud. Pseud. Serratia Klebsiella Proteus Proteus aureus Aronson aerugi- aerugi- marcesc. pneumon. mirabil. vulgaris nosa nosa SG 511 ATCC ATCC Hbg. ATCC ATCC ATCC Hbg. 9637 11775 10145 13880 10031 A 2.5 10 20 10 10 40 20 10 5 2.5 B 5 10 20 10 10 20 20 20 10 2.5 C 5 2.5 10 10 20 20 40 20 20 10 D 5 2.5 5 5 10 10 10 10 20 5 E 2.5 10 10 20 20 40 5 5 5 2.5 F 5 10 10 10 10 20 10 5 10 2.5 G 5 1.25 5 5 5 5 80 20 80 10 H 2.5 1.25 2.5 5 10 5 20 10 40 2.5 I 10 2.5 10 5 5 5 80 80 80 10 K 5 1.25 5 2.5 5 5 80 10 40 5 L 2.5 1.25 1.25 2.5 1.25 1.25 80 20 80 10 M 2.5 10 10 5 20 40 20 5 5 2.5 N 10 5 5 2.5 20 40 5 1.25 5 2.5 O 0.625 5 10 2.5 20 40 5 2.5 2.5 10 P 5 5 20 10 40 40 10 10 10 10 Q 20 10 20 20 20 20 5 10 10 5 R 5 2.5 10 10 40 40 20 10 20 10 The acute toxicity was determined by oral and subcutaneous application of the compounds to white laboratory mice in increasing doses.

The LD50 is the dose after which 50% of the animals are within die of 8 days. When administered orally, all substances showed an LD50 of over 2 g / kg, with subcutaneous administration an LD50 of well over 1 g / kg, i.e. at 2 g / kg or 1 g / kg, no animals died. They are therefore non-toxic in practice.

The active ingredients or the pharmaceutical preparations can be used locally, orally, parenterally, intraperitoneally and / or rectally, preferably orally or parenterally, such as intravenous or intramuscular administered.

The active ingredient or ingredients are used both in the human and in the Veterinary medicine advantageously in a dosage of about 5 to about 1000, preferably 10 to 200 mg / kg body weight per 24 hours, optionally in the form given in several single doses to achieve the desired results.

The individual dosage is generally about 1 to 250, preferably 10 to 60 mg / kg body weight. However, it may be required of the above Dosages vary, depending on the type and body weight the object to be treated, the nature and severity of the disease, the nature of the Preparation and application of the drug as well as the period or interval, within which the administration takes place. So it may be sufficient in some cases be able to manage with less than the abovementioned amount of active ingredient, while in in other cases the above-mentioned amount of active ingredient must be exceeded. The definition the required optimal dosage and type of application of the active ingredients can easily be done by any skilled person on the basis of their specialist knowledge.

The excellent antibacterial effect of the substances can be can also be detected in vivo.

For example, the compounds 4-N-ethyl-4 (R) -spectinomycylamine trihydrochloride, 4-N-propyl-4 (R) -spectinomycylamine trihydrochloride and 4-N-isopropyl-4 (R) -spectinomycylamine trihydrochloride effective substances for the treatment of infections in mammals, being the by Infections caused by gram-negative microorganisms are of particular concern.

To demonstrate the therapeutic effect, 7 groups of each 10 mice (female, 18-20 g, NMRI strain) with a culture of E. coli ATCC 11 775 infected intraperitoneally. Two groups remained untreated, the remaining 5 groups were administered subcutaneously 3 times a day on the 1st day and twice a day on the following 2 days different doses of the above substances to determine the ED50 (dose, in which 50% of the animals survive) treated.

The following table shows the ED50 values compared to spectinomycin. Compound ED50 (mg / kg sc) 4-N-ethyl-4 (R) -spectinomycylamine- trihydrochloride 8 4-N-Propyl-4 (R) -spectinomycylamine- trihydrochloride 7 4-N-Isopropyl-4 (R) -spectinomycylamine- trihydrochloride 9 Spectinomycin 20 The following examples describe the preparation of starting materials: Example A 6,8-bis-benzyloxycarbonyl-4-N-isopropyl-4 (R) -spectinomycylamine To a solution of 7.08 g (0.12 mol) of anhydrous isopropylamine in 60 ml of absolute methanol 20 ml (0.1 mol) of 5N methanolic hydrochloric acid are added with cooling.

Then, while stirring at room temperature, 12 g (0.02 mol) 6,8-bis-benzyloxycarbonyl-spectinomycin and, after cooling to 50 ° C., 1.25 g (0.02 Mol) sodium cyanoborohydride.

The reaction mixture is stirred at 50 ° C. for 2 hours, in 400 ml 0.5 Poured N aqueous hydrochloric acid and the resulting solution several times with ethyl acetate extracted.

After combining the ethyl acetate phases, these are mixed 3 times with 300ml each Water and 10 ml of 2N hydrochloric acid extracted.

The water extracts are made slightly alkaline (pH 8.5-9) and extracted this twice with 300 ml of methylene chloride each time, the organic phases are combined and dried these and evaporate them.

The remaining residue is purified by column chromatography (Silica gel 60, grain size 0.2-0.5 mm, E. Merck; mobile phase: chloroform + methanol = 5 + 1).

A colorless, amorphous powder with a decomposition area is obtained from 110-140 ° C.

Yield: 6.8 g (53% of theory) C33H45N3010 (643.75) Calc .: C 61.57 H 7.05 N 6.53 Found: 61.44 7.12 6.61 Molecular peak of the silylated Connection: M +: 859 = 643 + 3 x72 (3 silyl residues) In the same way were represented: a) 6,8-bis-benzyloxycarbonyl-4-N-methyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-spectinomycin, Methylamine hydrochloride and sodium cyanoborohydride.

Molecular peak of the silylated compound: M +: 831 = -615 + 3x72 (3rd Silyl residues) Calculated molecular weight: 615.69 b) 6,8-bis-benzyloxycarbonyl-4-N-ethyl-4 (R) -spectinomycylamine from 6, 8-bis-benzyloxycarbonyl-spectinomycin, ethylamine hydrochloride and sodium cyanoborohydride.

Molecular peak of the silylated compound: M +: 845 = 629 + 3x72 (3rd Silyl residues) Calculated molecular weight: -629.72 c) 6,8-bis-benzyloxycarbonyl-4-N-propyl-4 (R) -spectinomvcylamine from 6,8-bis-benzyloxycarbonyl-spectinomycn, propylamine hydrochloride and sodium cyanoborohydride.

Molecular peak of the silylated compound: M +: 859 = 643 + 3x72 (3rd Silyl residues) Calculated molecular weight: 643.75 d) 6, 8-bis-benzyloxycarbonyl-4-N-butyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-spectinomycin, Butylamine hydrochloride and sodium cyanoborohydride.

Molecular peak of the silylated compound: M +: 873 = 657 + 3x72 (3rd Silyl residues) Calculated molecular weight: 657.77 e) 6, 8-bis-benzyloxycarbonyl-4-N-isobutyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-spectinomycin, isobutylamine hydrochloride and sodium cyanoborohydride.

Molecular peak of the silylated compound: M +: 873 = 657 + 3x72 (3rd Silyl residues) Calculated molecular weight: 657.77 f) 6, 8-bis-benzyloxycarbonyl-4-N-aynyl-4 (R) -spectinomycvlamin from 6,8-bis-benzyloxycarbonyl-spectinomycin, amylamine hydrochloride and sodium cyanoborohydride.

Molecular peak of the silylated compound: M +: 887 2 671 + 3x72 (3 Silyl residues) Calculated molecular weight: 671.88 g) 6,8-bis-benzyloxycarbonyl-4-N-nonyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-spectinomycin, nonylamine hydrochloride and sodium cyanoborohydride.

Molecular peak of the silylated compound: M +: 943 = 727 + 3x72 (3 Silyl residues) Calculated molecular weight: 727.91 h) 6,8-bis-benzyloxycarbonyl-4-N-dodecyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-spectinomycin, dodecylamine hydrochloride and sodium cyanoborohydride.

Molecular peak of the silylated compound: M +: 985 = 769 + 3x72 (3rd Silyl radicals) Calculated molecular weight: 769.99 Example B 6, 8-Bis-benzyloxycarbonyl-4-N-ethyl-4 (R) -spectinomycylamine To a solution of 1.93 g (0.003 mol) 6,8-bis-benzyloxycarbonyl-4-N-acetyl-4 (R) -spectinomycylamine (made from 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and acetyl chloride) 1.13 g (0.03 mol) of sodium borohydride are added to 50 ml of absolute dioxane.

While stirring, one drips into the suspension at room temperature Solution of 2.3 ml (0.03 mol) of trifluoroacetic acid in 10 ml of dioxane, with vigorous foaming occurs.

The reaction mixture is then refluxed for 2 hours, cooled and poured into 250 ml of water.

It is extracted 3 times with 50 ml of methylene chloride each time, dried and distilled the solvent off.

The crude product is purified by column chromatography (Silica gel 60, grain size 0.2-0.5 mm, E. Merck; mobile phase: chloroform + methanol = 5 + 1).

A colorless, amorphous solid substance with a decomposition area is obtained from 105-130 ° C.

Yield: 0.96 g. ' (51% of theory) 32 43 3 10 (629.72) Ber .: C 61.03 H 6.88 N 6.67 Found: 60.88 6.97 6.51 Molecular peak of the silylated compound: M +: 845 = 629 + 3x72 (3 silyl residues) In the same way were prepared: a) 6,8-Bis-benzyloxycarbonyl-4-N-propyl-4 (R) -spectinomycylamine by reducing 6,8-bis-benzyloxycarbonyl-4-N-propionyl-4 (R) -spectinomycylamine with sodium borohydride / trifluoroacetic acid in dioxane.

Molecular peak of the silylated compound: M +: 859 = 643 + 3x72 (3rd Silyl radicals) Calculated molecular weight: 643.75 b) 6,8-bis-benzyloxycarbonyl-4-N-isobutyl-4 (R) -spectinomycylamine by reducing 6,8-bis-benzyloxycarbonyl-4-N-isobutyryl-4 (R) -spectinomycylamine with sodium borohydride / trifluoroacetic acid in dioxane.

Molecular peak of the silylietic compound: M +: 873 = 657 + 3x72 (3 Silyl residues) Calculated molecular weight: 657.77 c) 6,8-bis-benzyloxycarbonyl-4-N-amyl-4 (R) -spectinomycylamine by reduction of 6,8-bis-benzyloxycarbonyl-4-N-valeryl-4 (R) -spectinomycylamine with sodium borohydride / trifluoroacetic acid in dioxane.

Molecular peak of the silylated compound: M +: 887 = 671 + 3x72 (3rd Silyl residues) Calculated molecular weight: 671.88 d) 6,8-Bis-benzyloxycarbonyl-4-N-neopentyl-4 (R) -spectinomycylamine by reducing 6,8-bis-benzyloxycarbonyl-4-N-pivaloyl-4 (R) -spectinomycylamine with sodium borohydride / trifluoroacetic acid in dioxane.

Molecular peak of the silylated compound: M +: 887 = 671 + 3x72 ( 3 silyl residues) Calculated molecular weight: 671.88 e) 6, 8-bis-benzyloxycarbonyl-4-N-nonyl-4 (R) -spectinomycylamine by reduction of 6,8-bis-benzyloxycarbonyl-4-N-pelargonyl-4 (R) -spectinomycylamine with sodium borohydride / trifluoroacetic acid in dioxane.

Molecular peak of the silylated compound: M +: 943 = 727 + 3x72 (3 Silyl residues) Calculated molecular weight: 727.91 f) 6, 8-bis-benzyloxycarbonyl-4-N-dodecyl-4 (R) -spectinomycylamine by reducing 6,8-bis-benzyloxycarbonyl-4-N-lauryl-4 (R) -spectinomycylamine with sodium borohydride / trifluoroacetic acid in dioxane.

Molecular peak of the silylated compound: M +: 985 = 769 + 3x72 (3rd Silyl radicals) Calculated molecular weight: 769.99 g) 6,8-bis-benzyloxycarbonyl-4-N-hexadecyl-4 (R) -specti ~ omycYlamine by reduction of 6,8-bis-benzyloxycarbonyl-4-N-palmityl-4 (R) -spectinomycylamine with sodium borohydride / trifluoroacetic acid in dioxane.

Molecular peak of the silylated compound: M +: 1041 S 825 + 3x72 (3 Silyl residues) Calculated molecular weight: 826.10 h) 6,8-bis-benzyloxycarbonyl-4-N-octadecyl-4 (R) -spectinomycylamine by reduction of 6, 8-bis-benzyloxycarbonyl-4-N-stearyl-4 (spectinomycylamine with sodium borohydride / trifluoroacetic acid in dioxane.

Molecular peak of the silylated compound: M +: 1069 = 854 + 3x72 (3rd Silyl radicals) Calculated molecular weight: 854.15 Example C 6,8-Bis-benzyloxycarbonyl-4-N, N-dimethyl-4 (R) -spectinomycylamine To a stirred solution of 2.46 g (0.004 mol) 6,8-bis-benzyloxycarbonyl-4-N-methyl-4 (R) -spectinomycylamine and 1.5 g (0.02 mol) of 40% strength aqueous formaldehyde in 15 ml of acetonitrile becomes 0.4 added g (0.0064 mol) of sodium cyanoborohydride.

The reaction mixture is stirred for 15 minutes at room temperature.

Then neutralize with glacial acetic acid (tested against damp pH paper) and stir for a further 1.5 hours at room temperature. That solvent is distilled off in vacuo, the residue with 20 ml of 2N sodium hydroxide solution and 3 times with extracted 20 ml of methylene chloride each time. The combined organic phases are dried and concentrated in vacuo.

The remaining crude product is purified by column chromatography (silica gel 60, grain size 0.2-0.5 mm, E. Merck; Eluent: chloroform + methanol = 9 + 1).

The colorless, amorphous solid substance has a decomposition range of 950 to 12500.

Yield: 0.96 g (40% of theory) C32H43N3010 (629.72) Calculated: C 61.03 H 6.88 N 6.67 Found: 61.20 6.95 6.49 Molecular peak of the silylated compound: M +: 845 = 629 + 3x72 (3 silyl residues) The following were prepared in the same way: a) 6,8-bis-benzyloxycarbonyl-4-N-ethyl-4-N-methyl-4 (R) -spectinomycylamine by reductive methylation of 6,8-bis-benzyloxycarbonyl-4-N-ethyl-4 (R) -spectinomycylamine with formaldehyde / sodium cyanoborohydride.

'Molecular peak of the silylated compound: M +: 859 = 643 + 3x72 (3 Silyl radicals) Calculated molecular weight: 643.71 Example D 6, 8-bis-benzyloxycarbonyl-4-N- (4-dimethylaminobenzyl) -4 (R) -spectinomycylamine A solution from 3.6 g (0.006 mole) 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and 0.895 g (0.006 mol) of 4-dimethylaminobenzaldehyde in 30 ml of absolute ethanol are 5 hours stirred at room temperature.

After adding 3.6 g of platinum oxide, the reaction mixture is at room temperature Hydrogenated for 12 hours in a hydrogen pressure of 5 atm.

The catalyst is filtered off with suction and concentrated to dryness in vacuo and purifies the solid crude product by column chromatography. (Silica gel 60, grain size 0.2-0.5 mm, E. Merck; Mobile phase: chloroform + methanol = 20 + 1).

The colorless, amorphous solid substance has a decomposition range of 1200 to 1400C.

Yield: 2.94 g (66% of theory) C39H50N4010 (734.86) Calc .: C 63.74 H 6.86 N 7.62 Found: 63.52 6.94 7.39 Molecular peak of the silylated compound: M +: 950 =, 734 + 3x72 (3 silyl residues) In the same way were prepared: a) 6,8-bis-benzyloxycarbonyl-4-N- (Benzyl) -4 (R) -spectinomycylamine by reducing an ethanolic solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and benzaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 707 = 691 + 3x72 (3rd Silyl residues) Calculated molecular weight: 691.79 b) 6,8-bis-benzyloxycarbonyl-4-N- (4-methyl-benzyl) -4 (R) -spectinomycylamine by reducing an ethanolic solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and 4-methylbenzylaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 921 = 705 + 3 x72 (3 Silyl residues) Calculated molecular weight: 705.82 c) 6,8-Bis-benzyloxycarbonyl-4-N- (4-chlorobenzyl) -4 (R) -spectinomycylamine by reducing an ethanolic solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and 4-chloro-benzaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 941 = 725 + 3x72 (3 Silyl radicals) Calculated molecular weight: 725.23 d) 6,8-Bis-benzyloxycarbonyl-4-N- (3,4-dichlorobenzyl) -4 (R) -spectinomycylamine by reducing an ethanolic solution of 6,8-bisbenzyloxycarbonyl-4R) -spectinomycylamine and 3,4-dichlorobenzaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 976 = 760 + 3x72 (3rd Silyl residues) Calculated molecular weight: 760.69 e) 6, 8-bis-benzyloxycarbonyl-4-N- (4-methoxy-benzyl) -4 (R) -spectinomycylamine by reducing a Ethanol solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and 4-methoxybenzaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 937 = 721 + 3 x72 (3 Silyl residues) Calculated molecular weight: 721.82 f) 6,8-bis-benzyloxycarbonyl-4-N- (3,4,5-trimethoxybenzyl) -4 (R) -spectinomvcylamine by reducing an ethanolic Solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and 3,4,5-trimethoxy-benzaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 997 = 781 + 3x72 (3rd Silyl residues) Calculated molecular weight: 781.87 g) 6,8-Bis-benzyloxy-carbonyl-4-N- (3,4-methylenedioxy-benzyl) -4 (R) -spectinomycvlamin by reducing an ethanolic solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and 3,4-methylenedioxy-benzaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 951 = 735 + 3x72 (3rd Silyl residues) Calculated molecular weight: 735.80 h) 6,8-bis-benzyloxyearbonyl-4-N- (3-hydroxy-4-methoxy-benzyl) -4 (R) -spectinomycylamine by reducing an ethanolic solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and 3-hydroxy-4-methoxy -benzyldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 953 = 737 + 3x72 (3rd Silyl residues) Calculated molecular weight: 737.82 i) 6,8-bis-benzyloxycarbonyl-4-N- (4-hydroxy-benzyl) -4 (R) -spectinomycylamine by reducing an ethanolic solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and 4-hydroxybenzaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 923 = 707 + 3X72 (3rd Silyl residues) Calculated molecular weight: 707.79 k) 6,8-Bis-benzyloxycarbonyl-4-N- (4-acetaminobenzyl) -4 (R) -spectinomycylamine by reducing an ethanolic solution of 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and 4-acetaminobenzaldehyde with hydrogen in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 964 = 748 + 3x72 (3 Silyl residues) Calculated molecular weight: 748.85 Example E 6,8-Bis-benzyloxycarbonyl-4-N- (3-oxo) buty1--4 (R) -spectinomycylamine To a solution of 5.7 g (0.0095 mol) 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine in. 40 ml of absolute methanol at 400C 0.78 ml (0.0095 mol) Methyl vinyl ketone, dissolved in 10 ml of absolute methanol, was added dropwise with stirring. Man lets react for 1 hour at this temperature, evaporates to dryness in vacuo, dissolves the residue in 10 ml of 0.1 N hydrochloric acid and extracted twice with 30 ml of chloroform each time.

The organic phases are discarded. The aqueous layer becomes adjusted to pH 8.5 with 0.1 N sodium hydroxide solution and extracted 3 times with 30 ml of chloroform each time.

After drying and concentrating, the combined extracts remain a solid crude product that is purified by column chromatography (silica gel 60, Grain size 0.2-0.5 mm; E. Merck; Mobile phase: chloroform + methanol = 10 + 1).

The colorless, amorphous substance has a decomposition range of 1200-1450C.

Yield: 4.0 g (62% of theory) C34H45N3011 (671.76) Calc .: C 60.79 H 6.75 N 6.26 Found: 60.66 6.89 6.21 Molecular peak of the silylated compound: M +: 887 = 671 + 3x72 (3 silyl residues) In the same way, the following compounds Shown: a) 6, 8-Bis-benzyloxycarbonyl-4-N- (3-oxo) -pentyl-4 (R) -spectinomycylamine by addition of ethyl vinyl ketone to 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 901 = 685 + 3x72 (3 Silyl residues) Calculated molecular weight: 685.79 b) 6,8-bis-benzyloxycarbonyl-4-N- (4-methyl-oxo) Pentyl-4 (R) -spectinomycylamine by addition of i-propyl vinyl ketone to 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M + :, 915 = 699 + 3x72 (3 Silyl residues) Calculated molecular weight: 699.81 c) 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) -heptyl-4 (R) -spectiflomycylamine by addition of n-butyl vinyl ketone to 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 929 = 713 + 3x72 (3rd Silyl residues) Calculated molecular weight: 713.84 d) 6,8-bis-benzyloxycarbonyl-4-N- (4,4-dimethyl-3-oxo) -pentyl-4 (R) -spectiflomyclamine by addition of t-butyl vinyl ketone to 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 929 = 713 + 3x72 (3rd Silyl residues) Calculated molecular weight: 713.84 e) 6,8-Bis-benzyloxycarbonyl-4-N- (3-oxo) -undecyl-4 (R) -spectinomycylamine by addition of n-octyl vinyl ketone to 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 985 = 769 + 3x72 (3rd Silyl radicals) Calculated molecular weight: 769.95 Example F 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy) -butyl-4 (al-spectinomocylamine 1.3 g (0.0019 mol) 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) -butyl-4 (R) -spectinomycylamine, dissolved in 50 ml of absolute ethanol, with hydrogen in the presence of 0.26 g of platinum oxide hydrogenated at a pressure of 5 atm at room temperature for 12 hours.

The catalyst is filtered off with suction and evaporated to dryness in vacuo.

The remaining residue, an amorphous, colorless solid substance, is required no further cleaning. The melting range is between 1100 and 1850C.

Yield: 1.2 g (82% of theory) C34H47N3011 (673.77) Calc .: C 60.61 H 7.03 N 6.24 Found: 60.76 7.14 6.07 Molecular peak of the silylated compound: .4+: 889 = 673 + 3x72 (3 silyl residues) In the same way, the following compounds prepared: a) 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy) pentyl-4 (R) -spectinomycylamine by catalytic hydrogenation of 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) pentyl-4 (R) -spectinomycylamine in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 903 = 687 + 3x72 (3 Silyl residues) Calculated molecular weight: 687.80 b) 6,8-bis-benzyloxycarbonyl-4-N- (4-hydroxy-4-methyl) penthyl-4 (R) -spectinomycylamine by catalytic hydrogenation of 6,8-bis-benzyloxycarbonyl-4-N- (4-methyl-3-oxo) pentyl-4 (R) -spectinomycylamine in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 917 = 701- + 3x72 (3 Silyl residues) Calculated molecular weight: 701.83 c) 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy) heptyl-4 (R) -snectinomycylamine by catalytic hydrogenation of 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) heptyl-4 (R) -spectinomycylamine in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 931 = 715 + 3x72 (3rd Silyl residues) Calculated molecular weight: 715.86 d) 6, 8-bis-benzyloxycarbonyl-4-N- (4,4-Dimethyl-3-hydroxy) pentyl-4 (R) -spectinomycylamine by catalytic hydrogenation of 6,8-bis-benzyloxycarbonyl-4-N- (4,4-dimethyl-3-oxo) pentyl-4 (R) -spectinomycylamine in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 931 = 715 + 3x72 (3rd Silyl residues) Calculated molecular weight: 715.86 e) 6,8-Bis-benzyloxyearbonyl-4-N- (3-hydroxy) undecyl-4 (R) -spectinomycylamine by catalytic hydrogenation of 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) undecyl-4 (R) -spectinomycylamine in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 987 = 771 + 3x72 (3 Silyl residues) Calculated molecular weight: 771.96 f) 6,8-bis-benæyloxyearbonyl-4-N- (3-hydroxy-3-phenyl) -propyl-4 (R> -spectinomycylamine by catalytic hydrogenation of 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo-3-phenylpropyl-4 (R) -spectinomycylamine in the presence of platinum oxide.

Molecular peak of the silylated compound: M +: 951 = 735 + 3x72 (3rd Silyl radicals) Calculated molecular weight: 735.85 Example G 6,8-Bis-benzyloxycarbonyl-4-N- (4-methoxy) phenacyl-4 (R) -spectinomycylamine 3.6 g (0.006 mol) 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine, 1.47 g (0.0064 Mol) 4-methoxyphenacyl bromide and 840 mg of potassium carbonate are in 20 ml of acetonitrile Stirred for 20 hours at room temperature. The mixture is stirred into 150 ml of water and extracted with ethyl acetate. After drying, it is evaporated and the residue purified by column chromatography.

Yield: 1.4 g (31% of theory) Rf: 0.36 (silica gel, toluene / ethyl acetate = 1/4) In the same way there were obtained: a) 6,8-bis-benzyloxycarbonyl-4-N- (4-p-fluorophenyl) phenacyl-4fR) -spectinomycylamine the end 6,8-bis-bezyloxycarbonyl-4 (R) -spectinomycylamine and 4- (p-fluorophenyl) -phenacyl bromide Rf: 0.44 (silica gel, ethyl acetate) b) 6,8-bis-bezyloxycarbonyl-4-N - [(4-phenoxy) anilinocarbonyl] methyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid (4-phenoxy) anilide.

Rf: 0.48 (silica gel, methanol / chloroform = 1: 9) c) 4-N- / T4-xthoxy) anilinocarbonyl / methyl-6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine from 6,8-bis-bezyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid (4-ethoxy) anilide.

Rf: 0.50 (silica gel, methanol / chloroform 1: 9) d) 6,8-bis-benzyloxyearbonyl-4-N - / (4-methyl) anilinocarbonyl / methyl-4 (R) -spectinomycylamine from 6,8-bis-bezyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid p-toluidide.

Rf: 0.50 (silica gel, methanol / chloroform = 1: 9) e) 6,8-bis-benzyloxycarbonyl-4-N- (hexamethyleneiminocarbonyl) methyl-4 (R) -spectinomycylamine from 6,8-bis-bezyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid hexamethyleneimide.

Rf: 0.30 (silica gel, methanol / chloroform = 1: 9) f) 4-N - [(3-acetyl) - (4-ß-2-methoxyethoxy) anilinocarbonyl] methyl-6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine from 6,8-bis-bezyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid (3-acetyl-4-ß-methoxyethoxy) anilide.

Rf: 0.34 (silica gel, methanol / chloroform = 1: 3) g) 6t8-bis-benzyloxycarbonyl-4-N- (isopropylaminocarbonyl) methyl-4 (R) -spectinomycylamine from 6,8-bis-bezyloxycarbonyl-4 (R) -spectinomycylamine and isopropyl bromoacetic acid amide.

Rf: 0.30 (silica gel, methanol / chloroform = 1: 9) h) 6,8-bis-benzyloxycarbonyl-4-N - / (2-methoxyearbonyl) anilinocarbonyl] methyl-4 (R) -spectinomycylamine from 6,8-bis-bezyloxycarbonyl-4 (R) -spectinomycylamine and 4-bromoacetyl-2-aminobenzoic acid methyl ester Rf: 0.40 (silica gel, methanol / chloroform = 1:11) i) 6,8-bis-benzyloxycarbonyl-4-N- / Ñ'-methyl-N'-l1-methyl-2-hydroxy-2-phenyl ) ethylaminocarbonyl] methyl-4 (R) -spectinomycylamine from 6,8-bis-bezyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid-N-methyl-N- (2-hydroxy-2-phenyl-1-methyl) -ethylamide.

Rf: 0.59 (silica gel, methanol / chloroform = 1: 3) j) 4-N - / (4-ethoxyearbonyl) anilinocarbonyL / methyl-6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and N-bromoacetyl-anthranil-acid ethyl ester Rf: 0.59 (silica gel, methanol / chloroform = 1: 9) k) 6,8-bis-benzyloxycarbonyl-4-N- (methylaminocarbonyl) methyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and methyl bromoacetamide.

Rf: 0.50 (silica gel, methanol / chloroform = 1: 9)) 4-N- (benzylaminocarbonyl) methyl-6,8-bis-benzyloxycarbonyl-4 (R) -spectinomocylamine from 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid benzylamide.

Rf: 0.40 (silica gel, methanol / chloroform = 1: 9) m) 6,8-bis-benzyloxycarbonyl-4-N- (piperidinocarbonyl) methyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid piperidide.

Rf: 0.40 (silica gel, methanol / chloroform = 1: 9) n) 6,8-bis-benzyloxycarbonyl-4-N- (N'-methylanilinocarbonyl) methyl-4 (R) -spectinomycylamine from 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic acid N-methylanilide.

Rf: 0.60 (silica gel, chloroform / methanol = 9: 1) o) 4-N- (anilinocarbonyl) methyl-6,8-bis-benzyloxyearbonyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetic anilide.

Rf: 0.50 (silica gel, methanol / chloroform = 1: 9) p) 4-N- (SthOxyearbonyl) methyl-6,8-bis-benzyloxyearbonyl-4 (R) -spectinomycylamine 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and ethyl eromacetate.

Rf: 0.50 (silica gel, chloroform / methanol = 9: 1) q) 4-N - [(ethoxycarbonyl) -methylaminocarbonyl] methyl-6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine from 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and N-bromoacetyl-glycine ethyl ester.

Rf: 0.64 (silica gel, methanol / chloroform = 1: 5) r) 4-N- (3,5-dibromo-4-amino) phenacyl-6,8-bis (4-methoxy) -benzyloxycarbonyl-4 (R) -spectinomycylamine from 6,8-bis (4-methoxy) -benzyloxyearbonyl-4 (R) -spectinomycylamine and 4-amino-3,5-dibromo-phenacylbromide.

Rf: 0.29 (silica gel, chloroform / methanol = 5: 1) s) 4-N- (4-chloro) phenacyl-6,8-bis (4-methoxy) -benzyloxycarbonyl-4 (R) -spectinomycylamine from 6,8-bis (4-methoxy) -benzyloxyzarbonyl-4 (R) -spectinomycylamine and 4-chlorophenacyl bromide.

Rf: 0.80 (silica gel, chloroform / methanol 3: 1) t) 6,8-bis- (4-methoxy) -benzyloxycarbonyl-4-N- (2-oxo) -n-propyl-4 (R) - spectinomycylamine from 6,8-bis (4-methoxy) -benzyloxycarbonyl-4 (R) -spectinomycylamine and bromoacetone.

Rf: 0.29 (silica gel, chloroform / xethanol = 9: 1) example H 6,8-bis-benzyloxycarbonyl-4N-decanoyl-4 (R) -spectinomycylamine A solution of 1.25 g (0.0073 mol) of capric acid in 20 ml of methylene chloride is mixed with 1.00 ml (0.0073 mol) Triethylamine was added and the mixture was cooled to -10 ° C. 0.69 ml (0.0073 Mol) chloroformic acid ethyl ester and left for 30 minutes at this temperature. Then 4.0 g (0.0066 mol) of 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine, dissolved in 20 ml of methylene chloride, added. The reaction mixture is left without further Cooling to come to room temperature within one hour, whereby carbon dioxide escapes, shakes twice with 50 ml of water each time, dries and distills the methylene chloride in a vacuum.

The remaining solid crude product is purified by column chromatography (Silica gel 60, grain size 0.2-0.5 mm, E.

Merck; Mobile phase: methylene chloride + methanol = 18 + 1).

The substance obtained has a melting range of 125 ° -150 ° C.

Yield: 2.4 g (49% of theory) C40H57N3011 (755.92) Calc .: C 63.56 H 7.60 N 5.56 Found: 63.71 7.72 5.41 Molecular peak of the silylated compound: M +: 971 = 755 + 3x72 (3 silyl residues) The following were prepared in the same way: a) 6,8-bis-benzyloxycarbonyl-4-N-acetyl -4 (R) -ssectinomycylamine by reacting equimolar amounts of acetic acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 859 = 643 + 3x72 (3rd Silyl radicals) Calculated molecular weight: 643.70 b) 6, 8-bis-benzyloxycarbonyl-4-N-isobutyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of isobutyric acid and ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 887 = 671 + 3x72 (3rd Silyl residues) Calculated molecular weight: 671.76 c) 6,8-bis-benzyloxycarbonyl-4-N-caproyl-4 (R) -spectinonycylamine by reacting equimolar amounts of caproic acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 943 = 727 + 3x72 (3 Silyl residues) Calculated molecular weight: 727.87 d) 6,8-Bis-benzyloxycarbonyl-4-N-lauroyl-4fR) -spectinomycylamine by reacting equimolar amounts of lauric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 999 = 783 + 3x72 (3 Silyl residues) Calculated molecular weight: 783.97 e) 6, 8-BiS-benzyloxycarbpnyl-4-N-tridecanoyl-4 (R) -apectinomycyl'amine by reacting equimolar amounts of tridecanoic acid and ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1013 = 797 + 3x72 (3rd Silyl residues) Calculated molecular weight: 798.00 f) 6,8-Bis-benzyloxycarbonyl-4-N-palmitoyl-4 (R) -sPectinomycylamine by reacting equimolar amounts of palmitic acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1055 = 839 + 3x72 (3rd Silyl residues) Calculated molecular weight: 840.08 g) 6,8-bis-benzyloxycarbonyl-4-N-stearoyl-4 (R) -spectinomycylamine by reacting equimolar amounts of stearic acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1083 = 867 + 3x72 (3rd Silyl residues) Calculated molecular weight: 868.13 h) 6,8-bis-benzyloxycarbonyl-4-N-phenacetyl-4 (R) -spectinomycylamine by Implementation of equimolar amounts of phenylacetic acid, ethyl chloroformate and 6,8-bis-benzyloxyearbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 935 r 719 + 3x72 (3 Silyl residues) Calculated molecular weight: 719.76 i) 6,8-Bis-benzyloxycarbonyl-4-N-benzoyl-4 (R) -spectinomycylamine by reacting equimolar amounts of benzoic acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 921 = 705 + 3x72 (3rd Silyl residues) Calculated molecular weight: 705.77 k) 6,8-Bis-benzyloxycarbonyl-4-N- (Nt, N'-dimethyl) glycyl-4 (R) -spectinomycylamine by reacting equimolar amounts of N, N-dimethylglycine, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (spectinomycylamine.

Molecular peak of the silylated compound: M +: 904 = 686 + 3x72 (3 Silyl residues) Calculated molecular weight: 686.77 l) 6, 8-bis-benzyloxycarbonyl-4-N- (3-ethoxycarbonyl) propionyl-4 (R) -spectinomycylamine by converting equimolar Amounts of 3-ethoxycarbonyl-propionic acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 945 = 729 + 3x72 (3rd Silyl residues) Calculated molecular weight: 729.80 m) 6,8-bis-benzyloxycarbonyl-4-N- (4- / thylaminocarbonyl /) - butyryl-4 (R) -ssectinomycYlamine by reacting equimolar amounts of 4- (ethylaminocarbonyl) butyric acid, ethyl chloroformate and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 958 = 742 + 3x72 (3rd Silyl residues) Calculated molecular weight: 742.84 n) 6,8-Bis-benzyloxycarbonyl-4-N- (4- [isopropylaminocarbonyl]) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (isopropylaminocarbonyl) butyric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 972 = 756 + 3x72 (3rd Silyl residues) Calculated molecular weight: 756.87 o) 6,8-bis-benzyloxyearbonyl-4-N- (4- / ñ-hexylaminocarbonyl /) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (n-hexylaminocarbonyl) butyric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1014 = 798 + 3x72 (3rd Silyl residues) Calculated molecular weight: 798.95 p) 6,8-Bis-benzyloxycarbonyl-4-N- (4- [n-decylaminocarbonyl]) - butyryl-4 (R) -spectinomocylamine by reacting equimolar amounts of 4- (n-decylaminocarbonyl) butyric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1070 = 854 + 3x72 (3rd Silyl residues) Calculated molecular weight: 855.06 a) 6,8-Bis-benzyloxycarbonyl-4-N- (4-8dodecylaminocarbonyl /) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- 4- (dodecylaminocarbonyl) - butyric acid ethyl chloroformate and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1098 = 882 + 3x72 (3rd Silyl residues) Calculated molecular weight: 883.11 r) 6,8-Bis-benzyloxycarbonyl-4-N- (4- [tetradecylaminocarbonyl]) - butyryl-4 (R) -spectinomycylamine, by reacting equimolar amounts of 4- (tetradecylaminocarbonyl) butyric acid, ethyl chloroformate and 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1126 = 910 + 3x72 (3rd Silyl residues) Calculated molecular weight: 911.16 s) 6,8-Bis-benzyloxyearbonyl-4-N- (4-Lõctadecylaminocarbonyl /) - butyryl- (R) -spectinomycylamine by reacting equimolar amounts of 4- (octadecylaminocarbonyl) butyric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine, molecular peak of the silylated Compound: M +: 1182 = 966 + 3x72 (3 silyl residues) Calculated molecular weight: 967.27 t) 6,8-bis-benzyloxyearbonyl-4-N- (4- / benzylaminocarbonyl /) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (benzylaminocarbonyl) butyric acid ethyl chloroformate and 6,6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1020 = 804 + 3x72 (3rd Silyl residues) Calculated molecular weight: 80d, 91 u) 6,8-bis-benzyloxycarbonyl-4-N- (4- / phenylaminocarbonyl /) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (phenylaminocarbonyl) -butyric acid, Ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1006 = 790 + 3x72 (3rd Silyl residues) Calculated molecular weight: 790.88 v) 6,8-Bis-benzyloxyearbonyl-4-N- (4- / diethylaminocarbonyl /) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (diethylaminocarbonyl) -butter acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 986 = 770 + 3x72 (3rd Silyl residues) Calculated molecular weight: 770.89 w) 6,8-bis-benzyloxycarbonyl-4-N- (4- [dihexylaminocarbonyl]) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (dihexylaminocarbonyl) butyric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbony 2-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1098 = 882 + 3x72 (3rd Silyl residues) Calculated molecular weight: 883.11 x) 6,8-Pis-benzyloxycarbonyl-4-N- (4- / iibenzylaminocarbonyl / ) -butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (dibenzylaminocarbonyl) butyric acid, Ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1110 = 894 + 3x72 (3rd Silyl residues) Calculated molecular weight: 895.04 y) 6,8-Bis-benzyloxycarbonyl-4-N- (4- [pyrrolidinocarbonyl]) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (pyrrolidinocarbonyl> -butyric acid, ethyl chloroformate and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 984 = 768 + 3x72 (3rd Silyl residues) Calculated molecular weight: 768.88 z) 6t8-Bis-benzyloxycarbonyl-4-N- (4-2morpholinocarbonyl /) - butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (morpholinocarbonyl) butyric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1000 = 784 + 3x72 (3 Silyl residues) Calculated molecular weight: 784.88 aa) 6,8-bis-benzyloxycarbonyl-4-N- (4- hiomorpholincarbonyl /) - butyryl-4 (R) -spectinomycylamine by conversion of equimolar Amounts of 4- (thiomorpholinocarbonyl) butyric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1016 = 800 + 3x72 (3rd Silyl residues).

Calculated molecular weight: 800.94 ab) 6,8-bis-benzyloxycarbonyl-4-N- (4 - [{4-benzyl} piperidinocarbonyl]) butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (4-benzyl) piperidinocarbonyl-butyric acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1088 = 872 + 3x72 (3rd Silyl residues) Calculated molecular weight: 873.03 ac) 6,8-bis-benzyloxycarbonyl-4-N- (3-8dodecylaminocarbonyl /) -propionyl-4 (R) -spectinomycylamine by reacting equimolar amounts of 3- (Dodecylaminocarbonvl) propionic acid, ethyl chloroformate and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1084 = 868 + 3x72 (3rd Silyl residues) Calculated molecular weight: 869.08 ad) 6,8-bis-benzyloxycarbonyl-4-N- (5- / dodecylaminocarbonyl /) - valeryl-4 (R) - spectinomycylamine by reacting equimolar amounts of 5- (dodecylaminocarbonyl) valeric acid, ethyl chloroformate and 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1112 = 896 + 3x72 (3rd Silyl residues) Calculated molecular weight: 897.14 ae) 6,8-bis-benzyloxycarbonyl-4-N- (4- [dodecylaminocarbonyl)] -benzoyl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4- (dodecylaminocarbonyl) benzoic acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1132 = 916 + 3x72 (3rd Silyl residues) Calculated molecular weight: 917.13 af) 6, 8-bis-benzyloxycarbonyl-4-N- (4-cyano> butyryl-4 (R) -spectinomycylamine by reacting equimolar amounts of 4-cyanobutyric acid, Ethyl chloroformate and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 912 = 696 + 3x72 (3rd Silyl residues) Calculated molecular weight: 696.77 ag) 6,8-bis- (4-methoxy) benzyloxycarbonyl-4-N- (3- / N'-methyl-N'-dodecyl / -aminocarbonyl) cropionyl-4 (R) -spectinomycYlamine from 6,8-bis (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomycylamine and succinic acid-N-methyl-N-dodecyl-monoamide.

Rf: 0.65 (silica gel, chloroform / methanol = 3: 1) ah) 1,4-bis- [6,8-bis- (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomycyl- (4) -aminocarbonyl] ]-butane the end 6,8-bis (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomyCylamine and adipic acid.

Rf: 0.76 (silica gel, chloroform / methanol = 3: 1) ai) 1,7-bis- / 6,8-bis- (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomycyl- (4) -aminocarbonyl ] -3-oxo-4-aza-heptane from 6,8-bis (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomyCylamine and succinic acid-mono-n-propylamide.

Rf: 0.69 (silica gel, chloroform / methanol = 3: 1) ak) 4-N- (5-benzoyl) valeroyl-6,8-bis- (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomycylamine from 6,8-bis- (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomycylamine and 5-benzoylvaleric acid.

Rf: 0.75 (silica gel, chloroform / methanol = 3: 1) al) 4-N- (4-n-hexylaminocarbonyl) benzoyl-6,8-bis (4-methoxy) benzyloxycarbonyl-rl ( R) -spectinomycylamine from 6,8-bis- (4-methoxy) benzyloxyearbonyl-4 (R) -spectinomycylamine and terephthalic acid mono-n-hexylamide.

Rf: 0.80 (silica gel, chloroform / methanol = 3: 1) am) 4-N- / 4- (aminocarbonyl) -methylaminocarbonyl / butyryl-6,8-bis (4-methoxy) benzyloxyearbonyl-4 (R) -spectinomycylamine from 6,8-bis (4-methoxy) benzyloxyearbonyl-4 (R) -spectinomycylamine and glutaric acid-mono- (aminocarbonyl) -methylamide.

Rf: 0.39 (silica gel, chloroform / ethanol = 3: 1) an) 4-N- / 4- (N'-methylpiperazinocarbonyl) butyryl-6,8-bis (4-methoxy) -benzyloxycarbonyl-4 (R) -spectinomycylamine the end 6,8-bis (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomycylamine and glutaric acid mono- (N '-methyl) piperazide.

Rf: 0.44 (silica gel, chloroform / methanol = 3: 1) Example I 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) glycyl-4 (R) -spectinomycylamine A solution of 1.0 g (0.005 mol) of N-benzyloxycarbonylglycine and 0.60 g of N-hydroxysuccinimide in 30 ml of absolute methylene chloride are cooled with ice mixed with 1.1 g of dicyclohexylcarbidiimide. The mixture is left at 5 ° C overnight stirred and then sucked off the resulting dicyclohexylurea. The filtrate becomes a solution of 3.0 g (0.005 mol) 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine at room temperature dropped into 20 ml of methylene chloride. The reaction solution is left at room temperature for 6 hours stirred and then concentrated to dryness.

The finished product obtained is purified by column chromatography (Silica gel 60, grain size 0.2-0.5 mm, E. Merck; mobile phase: methylene chloride + Methanol = 20 + 1).

The substance obtained decomposes above 1150C.

Yield: 3.7 g (46.5% of theory) of C40H48N4013 (792.86) molecular peak of the silylated compound: M +: 936 = 792 + 2x72 (2 silyl residues) In the same way were shown: a) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) -β-alanyl-4 (R) -spectinomycylamine by Implementation of equimolar amounts of the succinimide ester of N-benzyloxycarbonyl-ß-alanine and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 950 = 806 + 2x72 (2 Silyl residues) Calculated molecular weight: 806.88 b) 6, 8-bis-benzyloxycarbonyl-4-N- (N1 -benzyloxycarbonyl) -? - amirioburyrvl-4 (R) -spectinomycvlamin by reaction equimolar amounts of the succinimide ester of N-benzyloxycarbonyl-γ-aminobutyric acid and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine molecular peak of the silylated Compound: M +: 964 = 820 + 2x72 (2 silyl residues) Calculated molecular weight: 820.91 c) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) isoseryl-4 (R) -spectinomycylamine by reacting equimolar amounts of the succinimide ester of N-benzyloxycarbonyl-D, L-isoserine and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

The two diastereoisomers can be separated by column chromatography (silica gel, methylene chloride + methanol = 10 + 1).

Both show the same molecular peak in the mass spectrum: M +: 1038 = 822 + 3x72 (3 silyl residues) Calculated molecular weight: 822.88 d) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonylamino-2 ' hydrpxy) butyrvl - $ (R) -spectinomycylamine by reacting equimolar amounts of the Succinimide esters of L-4-benzyloxycarbonylamino-2-hydroxy-butyric acid and 6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine Molecular peak of the silylated compound: M +: 1050 = 834 + 3x72 (3 silyl residues) Calculated molecular weight: 834.91 e) 6,8-bis-benzyloxycarbonyl-4-N- (N'-acetyl) glycyl-4 (R) -spectinomycylamine by reacting equimolar amounts of N-acetylaminoacetic acid, ethyl chloroformate and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 842 = 698 + 2x72 (2 Silyl residues) Calculated molecular weight: 698.74 f) 6,8-Bis-benzyloxyearbonyl-4-N- (N'-methyl-N'-acetyl) glycyl-4 (R) -spectinomycylamine by reacting equimolar amounts of N-acetyl-N-methylaminoacetic acid, dicylcohexylcarbodiimide and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 856 = 712 + 2x72 (2 Silyl residues) Calculated molecular weight: 712.77 g) 6,8-bis-benzyloxycarbonyl-4-N- ( 5- '-dodecyl7amino) valeryl-4 (R) -stectinomycylamine by conversion of equimolar Amounts of the succinimide ester of 5-dodecylamino-valeric acid and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1112 = 896 + 3x72 (3rd Silyl residues) Calculated molecular weight: 897.14 h) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzoyl) glycyl-4 (R) -spectinomycylamine by Conversion of equimolar amounts of hippuric acid N-hydroxysuccinimide ester and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 906 = 762 + 2x72 (2 Silyl residues) Calculated molecular weight: 762.46 i) 6,8-bis-benzyloxyearbonyl-4-N- (N'-ethylcarbamoyl) isoseryl-4 (R) -spectinomycylamine by reacting equimolar amounts of the succinimide ester of N-ethylcarbamoyl-D, L-isoserine and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

The two diastereomers can be separated by column chromatography (Silica gel, methylene chloride: methanol 13: 1) Both show the same molecular peak in the mass spectrum M +: 975 = 759 + 3x72 (3 silyl residues) Calculated molecular weight: 759.82 k) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) -D-alanyl-4 (R) -spectinomycylamine by reacting equimolar amounts of the succinimide ester of benzyloxycarbonyl-D-alanine and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 950 = 806 + 2x72 (2 Silyl radicals) Calculated molecular weight: 806.88 1) 6,8-Bis-benzyloxyearbonyl-4-N- (2'-benzyloxycarbonylamino) -valeroyl-4 (R) -spectinomycylamine by converting equimolar amounts of the succinimide ester of benzyloxycarbonyl-norvaline and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 978 = 834 + 2x72 (2 Silyl residues) Calculated molecular weight: 834.94 m) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl-3'-phenyl) -β-alanyl-4 (R) -spectinomycylamine by reacting equimolar amounts of the succinimide ester of N-benzoyloxycarbonyl-3-phenyl-ß-alanine and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1026 = 882 + 2x72 (2 Silyl radicals) Calculated molecular weight: 882.98 n) 6,8-Dis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl-m, m'-dichloro-P-amino) phenylqlycyl-4 (R) -spectinomycylamine by reacting equimolar amounts of the succinimide ester of N-benzyl-oxyearbonyl-m, m'-aichlor-p-amino-D, L-phenylglycine and 6,8-bis-benzyloxyearbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1168 = 952 + 3x72 (3rd Silyl residues) Calculated molecular weight: 952.87 o) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) -D-seryl-4 (R) -spectinomycylamine by reacting equimolar amounts of the succinimide ester of N-benzyloxycarbonal-D-serine with 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 1038 = 822 + 3x72 (3rd Silyl residues) Calculated molecular weight: 822.88 p) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl-N'-methyl) -β-alanyl-4 (R) -spectinomycylamine by reacting equimolar amounts of the succinimide ester of N-benzoyloxycarbonyl-N-methyl-ß-alanine and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 966 = 820 + 2x72 (2 Silyl radicals) Calculated molecular weight: 820.91 q) 6,8-bis-benzyloxycarbonyl-4-N- (N'-dimethyl) -β-alanyl-4 (R) -spec ctinomycylamine by reacting equimolar amounts of the succinimide ester of N, N-dimethyl-ß-alanine and 6, 8-bis-benzyloxycarbonyl-4 (R) -spectinomyclamine.

Molecular peak of the silylated compound: M +: 980 = 834 + 2x72 (2 Silyl residues) Calculated molecular weight: 834.94 r) 6, 8-bis-benzyloxycarbonyl-4-N - ( ß-pyrrolidino) propionyl-4 (R) -spectinomycylamine by reacting equimolar amounts of the succinimide ester of ß-pyrrolidino-propionic acid and 6,8-bis-benzyloxycarbonyl-4 (R) -sp ctinomycylamine.

Molecular peak of the silylated compound: M +: 870 = 726 + 2x72 (2 Silyl residues) Calculated molecular weight: 726.84 s) 6,8-bis-benzyloxycarbonyl-4-N- (β- [4'-benzylpiperidino]) propionyl-4 (R) -spectromycylamine by Implementation of equimolar amounts of the succinimide ester of ß- (4-benzyl-piperidino) -propionic acid and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

M +: 976 = 832 + 2x72 (2 silyl residues) Calculated molecular weight: 833.01 t) 6 6,8-bis-benzyloxyzarbonyl-4-N- (β-morpholino) propionyl-4 <R) -spectinomycvlamin by converting equimolar amounts of the succinimide ester of ß-morpholino-propionic acid and 6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine.

Molecular peak of the silylated compound: M +: 886 = 742 + 2x72 (2 Silyl residues) Calculated molecular weight: 742.84 u) 6, 8-bis-benzyloxycarbonyl-4-N- (ß- / 41 -methyl-piperazino /) propionyl-4 (R) -spectromycylamine by reaction of equimolar Amounts of the succinimide ester of ß- (4'-methyl-piperidino) -propionic acid and 6,8-bis-benzyloxycarbonyl-4 (R) -specinomycylamine.

Molecular peak of the silylated compound: M +: 899 = 755 + 2x72 (2 Silyl residues) Calculated molecular weight: 755.88 The following Examples describe the production of the end products: Example 1 4-N-Isopropyl-4 (Ft) -sDectinomycyl-amine-trihydrochloride 2.0 g (0.003 mol) 6,8-bis-benzyloxycarbonyl-4-N-isopropyl-4 (R) -spectinomycylamine, dissolved in 25 ml of 3% ethanolic hydrochloric acid in the presence of 1 g of palladium-carbon (10%) with hydrogen for 2 hours under normal conditions (1 atm, room temperature) hydrogenated.

The catalyst is separated off and the solvent is evaporated off in vacuo and dries in a high vacuum.

The solid product obtained is analytically pure.

Yield: 1.35 g (94% of theory) F .: 1650C (dec.) C17 33 3 6 x3HCl (484.87) Calc .: C 42.11 H 7.48 N 8.67 Found: 41.98 7.37 8.79 In the same manner synthesized the following compounds: a) 4-N-methyl-4 (R) -spectinomyclamine trihydrochloride by reduction of 6, 8-bis-benzyloxycarbonyl-4-N-methyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (109sig) in ethanolic hydrochloric acid.

F .: 12500 (decomp.) b) 4-N-Ethyl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N-ethyl-4 (R) -spectinomycylamine with Hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1600C (dec.) C) 4-N-Propyl-4 (R) -spectinomyclamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-propyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1500C (decomp.) D) 4-N-Butyl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N-butyl-4 (R) -spectinomycylamine with Hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1700C (dec.) E) 4-N-Isobutyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-isobutyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 165 ° C (dec.) F) 4-N-Amyl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N-amyl-4 (R) -spectinomycylamine with Hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 17500 (decomp.) b) 4-N-Nonyl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N-nonyl-4 (R) -spectinomycylamine with Hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1650C (dec.) H) 4-N-dodecyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-dodecyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 1700C (dec.) I) 4-N-neonentyl-4 (R) -spectihomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-neopentyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1550C (dec.) K) 4-N-hexadecyl-4 (R) -spect-inomocylamine-trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-hexadecyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1500C (dec.) L) 4-N-octadecyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-octadecyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1700C (dec.) m) 4-N, N-dimethyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N, N-dimethyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1600C (dec.) N) 4-N-xthYl-4-N-methol-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-ethyl-4-N-methyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 175 ° C (dec.) O) 4-N- (4-Dimethylaminobenzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of 6, 8-bis-benzyloxycarbonyl-4-N- (4-dimethylamino-benzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1800C (dec.) P) 4-N-Benzyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-benzyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 170 ° C (dec.) Q) 4-N- (4-methyl-benzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4-methylbenzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F.:175°C (dec.) r) 4-N- (4-chlorobenzyl) -4 (R) spe'ctinomycylamine trihydrochloride by reducing 6, 8-bis-benzyloxycarbonyl-4-N- (4-chlorobenzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1800C (dec.) S) 4-N- (3t4-dichlorobenzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3,4-dichlorobenzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 16500 (dec.) T) 4-N- (4-methoxy-benzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4-methyoxy-benzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 17500 (dec.) U) 4-N- (3,4,5-trimethoxy-benzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3,4,5-trimethoxy-benzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1600C (dec.) V) 4-N- (3,4-methylenedioxy-benzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of, 8-bis-benzyloxycarbonyl-4-N- (3,4-methylenedioxy-benzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 18700 (decomp.) w) 4-N- (3-Hydroxy-4-methoxy-benzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy-4-methoxy-benzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1750C (dec.) X) 4-N- (4-Hydroxy-benzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4-hydroxybenzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1850C (dec.) Y) 4-N- (4-acetaminobenzyl) -4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4-acetaminobenzyl) -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1800C (dec.) Z) 4-N- (3-Oxo) butvl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) -butyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1500C (decomp.) Aa) 4-N- (3-oxo) pentyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) -euentyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1650C (dec.) ab) 4-N- (4-methyl-3-oxo) pentyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4-methyl-3-oxo) pentyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 1400C (dec.) Ac) 4-N- (3-Oxo) hentyl-4 (R) -seectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) -heptyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 1550C (dec.) Ad) 4-N- (4,4-dimethyl-3-oxo) pentyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4,4-dimethyl-3-oxo) pentyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 1450C (dec.) Ae) 4-N- (3-Oxo) undecyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-oxo) undecyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 170 ° C (dec.) Af) 4-N- (3-hydroxy) butyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy) butyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1600C (decomp.) ag) 4-N- (3-hydroxy) pentyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy) pentyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 125 ° C (dec.) Ah) 4-N- (3-Hydroxy-4-methyl) pentyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy-4-methyl) pentyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (109sig) in ethanolic hydrochloric acid.

Q .: 16500 (dec.) Ai) 4-N- (3-hydroxy) heptyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy) heptyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (109sig) in ethanolic hydrochloric acid.

M.p .: 130 ° C (decomp.) 4-N- (4,4-dimethyl-3-hydroxy) pentyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4,4-dimethyl-3-hydroxy) pentyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (1096ig) in ethanolic hydrochloric acid.

F .: 17500 (decomp.) al) 4-N- (3-Hydroxy) undecyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy) undecyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 160 ° C (dec.) Am) 4-N- (3-Hydroxy3-phenyl) propyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3-hydroxy-3-phenyl) propyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (1096ig) in ethanolic hydrochloric acid.

F .: 185 ° C (dec.

an) 4-N-decanoyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-decanoyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 175 ° C (dec.) Ao) 4-N-acetyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-acetyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 170 ° C (dec.) Ap) 4-N-isobutyryl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N-isobutyryl -4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 160 ° C (dec.) Aq) 4-N-Caproyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-caproyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 155 ° C (dec.) Ar) 4-N-Lauroyl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N-lauroyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 150 ° C (dec.) As) 4-N-Tridecanovl-4 (R) -snectinomycolamine-trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-tridecanoyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 165 ° C (dec.) At) 4-N-palmitoyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-palmitoyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1300C (dec.) au) 4-N-stearoyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-stearoyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 1400C (dec.) Av) 4-N- (Phenyl) acetyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4 - (phenyl) -acetyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1700C (dec.) Aw) 4-Benzoyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N-benzoyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 1450C (dec.) Ax) 4-N- (N ', N'-dimethyl) glycyl-4 (R) -spectinomycylamine-trihydro chloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N ", N'-dimethyl) glycyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 125 ° C (dec.) Ay) 4-N- (3-sthoxycarbonyl) propionyl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N- (3-ethoxycarbonyl ) propionyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (1096ig) in ethanolic hydrochloric acid.

M.p .: 150 ° C (dec.) Az) 4-N- (4- [ethylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [äthylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium crude (10%) in ethanol Hydrochloric acid m.p .: 135 ° C (dec.) Ba) 4-N- (4- [Isopropylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [isopropylaminocarbonyi /) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 160 ° C (dec.) Bb) 4-N- (4- [hexylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [hexylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 130 ° C (dec.) Bc) 4-M- (4-8decylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine trihydrochloride by Reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4-decylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 135 ° C (dec.) Bd) 4-N- (4- / dodecylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N- (4- [dodecylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 140 ° C (dec.) Be) 4-N- (4- / tetradecylaminocarbonyl /) butyryl-4 (R) -spectinomyCylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [tetradecylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 145 ° C (dec.) Bf) 4-N- (4- [Octadecylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [octadecylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1500C (decomp.) bg) 4-N- (4-BenzylaminocarbonyJl ) butyryl-4 (R) -spectinomycylamine-trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [benzylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 140 ° C (dec.) Bh) 4-N- (4- / phenylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [phenylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 135 ° C (dec.) Bi) 4-N- (4- / diethylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [diethylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 150 ° C (dec.) Bk) 4-N- (4- / dihexylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [dihexylaminocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 13500 (decomp.) bl) 4-N- (4- / dibenzylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- / dibenzylaminocarbonyl /) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%), in ethanolic hydrochloric acid.

M.p .: 135 ° C (dec.) Bm) 4-N- (4- [Pyrrolidinocarbonyl]) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [pyrrolidinocarbony1 /) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 140 ° C (decomp.) Bn) 4-N- (4- / Morpholinocarbony1 /) butyryl- $ (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- [morpholinocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 150 ° C (dec.) Bo) 4-N- (4- [Thiomorpholinocarbonyl]) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- / thiomorpholinocarbonyl /) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 135 ° C (dec.) bp) 4-N- (4 - [{4-Benzyl} piperidinocarbonyl]) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4 - [{4-benzyl} piperidinocarbonyl]) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 145 ° C (dec.) Bq) 4-N- (3- / dodecylaminocarbonyl /) propionyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (3- / dodecylaminocarbonyl /) propionyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanol Hydrochloric acid.

M.p .: 140 ° C (dec.) Br) 4-N- (5- / dodecylaminocarbonyl /) valeryl-4 (R) -spectinomycylamine-trihydro chloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (5- / dodecylaminocarbonyl /) valeryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1500C (decomp.) Bs) 4-N- (4- / dodecylaminocarbonyl /) benzoyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4- / dodecylaminocarbonyl /) benzoxyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1600C (decomp.) bt) 4-N- (5- / N-dodecyl / amino) valeryl4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (5- [N'-dodecyl / amino-) valeryl-4 (R) -spectinQmycylamine with hydrogen and palladium-carbon (10%) in ethanol Hydrochloric acid.

M.p .: 165 ° C (dec.) Bu) 4-N- (anilinocarbonyl) methyl-4- (R) -spectionomycylamine trihydrochloride from 4-N- (anilinocarbonyl) l-ethyl-6,8-bis-benzyloxyearbonyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

F .: 175-180 ° C (dec.) Bv) 4-N- (piperidinocarbonyl) methyl-4 (R) -spectinomycylamine trihydrochloride from 6,8-bis-benzyloxycarbonyl-4-N- (piperidinocarbonyl) methyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

F .: 1800C (dec.) Bw) 4-N- (N'-methylanilinocarbonyl) methyl-4 (R) -spectionomycylamine trihydrochloride from 6,8-bis-benzyloxycarbonyl-4-N- (N2-methylanilinocarbonyl) -methyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

Q .: 170-175 C (dec.) Bx) 4-N - [(4-phenoxy) anilinocarbonyl) methyl-4 (R) -spectionomycylamine trihydrochloride the end 6,8-bis-benzyloxycarbonyl-4-N - [(4-phenoxy) anilinocarbonyl) methyl-4 (R) -spectionomycylamine and palladium-carbon in ethanolic hydrochloric acid.

M.p .: 180 ° C (decomp.) Bz) 4-N - [(4-ethoxy) anilinocarbonyl) methyl-4 (R) -spectionomycylamine trihydrochloride 4-N - [(4-ethoxy) anilinocarbonyl) methyl-6,8-bis-benzyloxycarbonyl-4 (R) -spectionomycylamine and palladium-carbon in ethanolic hydrochloric acid.

F. 175-180 C (dec.) Ca) 4-N - [(4-methyl) anilinocarbonyl) methyl-4 (R) -spectionomycylamine trihydrochloride from 6,8-bis-benzyloxycarbonyl-4-N - / (4-methyl) anilinocarbonyl) methyl-4 (R) -spectionomycylamine and palladium-carbon in ethanolic hydrochloric acid.

F .: 180-185 ° C (dec.) Cb) 4-N- (hexamethyleneiminocarbonyl) methyl-4 (R) -spectionomycylamine trihydric chloride from 6,8-bis-benzyloxycarbonyl-4-N- (hexamethyleneiminocarbonyl) -methyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

F .: 170-175 C (dec.) Cc) 4-N - [(3-acetyl) - (4-β-methoxyethoxy) anilinocarbony] methyl 4 (R) -spectionomycylamine trihydrochloride from 4-N - [(3-acetyl) - (4-ß-methoxyethoxy) anilinocarbony] methvl-6 r 8-bis-benzyloxyearbonyl-4 (R) -spectinomycylamine and Palladium-carbon in ethanolic hydrochloric acid.

M.p .: 173-175 ° C (dec.) Cd) 4-N- (Isopropylaminocarbonyl) methyl-4 (R) -spectinomycylamine trihydrochloride from 6,8-bis-benzyloxycarbonyl-4-N- (isopropylaminocarbonyl) methy-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

Q .: 165-1700C (dec.) Ce) 4-N - [(2-methoxycarbonyl) anilinocarbonyl] methyl-4 (R) -spectinomycylamine trihydrochloride from 6,8-bis-benzyloxyearbonyl-4-N - / (2-methoxyearbonyl) anilinocarbonyl] methyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

Rf .: 0.37 (silica gel, methanol / chloroform / ammonia = 20/20/2) cf) 4-N- [N'-methyl-N '- (1-methyl-2-hydroxy-2-phenyl) -ethylaminocarbonyl] methyl-4 (R) -spectinomycylamine trihydrochloride from 6,8-bis-benzyloxycarbonyl-4-N-8N 'methyl-N' - (1-mXethyl-2-hydroxy-2-phenyl) -ethylaminocarbonyl] methyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

Rf .: 0.40 (silica gel, alcohol / chloroform / ammonia = 20/20/2) cg) 4-N - [(4-Ethoxycarbonyl) anilinocarbonyl] methyl-4 (R) -spectinomycvlamine trihydrochloride from 4-N-d, (4-ethoxyearbonyl) anilinocarbonyl / methyl-6,8-bisbenzyloxycarbonyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

Rf .: 0.74 (silica gel, methanol / chloroform / ammonia = 20/20/2) ch) 4-N- (methylaminocarbonyl) methyl-4 (R) -spectinomyCylamine trihydrochloride from 6,8-bis-benzyloxycarbonyl-4-N- (methylaminocarbonyl) methyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

F .: 170-175 ° C (dec.) Ci) 4-N- (Benzylaminocarbonyl) methyl-4 (R) -spectinomycylamine-trihyrochloride from 6,8-bis-benzyloxyearbonyl-4-N- (benzylaminocarbonyl) methyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

F .: 170-175 ° C (dec.) Ck) 4-N - / (Ethoxyzarbonyl) -methylaminocarbonylZmethyl-4 (R) -spec t; nomycyl amine trihydro chloride from 4-N - [(ethoxycarbonyl) -methyl-aminocarbonyl] methyl-6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

Rf .: 0.50 (silica gel, methanol / chloroform / ammonia = 20/20/2).

cl) 4-N- (4-methoxy) phenacyl-4 (R) -spectinomycylamine trihydrochloride from 6,8-bis-benzyloxyearbonyl-4-N- (4-methoxy) phenacyl-4 (R) -spectinomycylamine and Palladium / barium sulfate in ethanol.

Rf .: 0.38 (silica gel, chloroform / methanol / ammonia = 20/20/4).

cm) 4-N- (4-p-fluorophenyl) -phenacyl-4 (R) -spectinomycylamine trihydrochloride the end 6,8-bis-benzyloxycarbonyl-4-N- (4-p-fluorophenyl) phenacyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

Rf .: 0.36 (silica gel, chloroform / methanol / ammonia = 20/20/3) cn) 4-N- (Athoxycarbonyl) methyl-4 (R) -spectinomycylamine trihydrochloride from 4-N- (Athoxycarbonyl) methyl-6,8-bis-benzyloxycarbonyl-4 (R) -spectinomycylamine and palladium-carbon in ethanolic hydrochloric acid.

F .: 155-1600C (dec.) Example 2 4-N-Glycyl-4 (R) -spectrinomycylamine trihydrochloride 2.4 g (0.003 mol) 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) -glycyl-4 (R) -spectinomycylamine, dissolved in 35 ml of 3% ethanolic hydrochloric acid in the presence of 1 g of palladium-carbon (10%) hydrogenated with hydrogen under normal conditions (1 atm, room temperature), until an IR spectrum of a sample shows the complete cleavage of the protective groups.

The catalyst is separated off and the solvent is evaporated off in vacuo and dries in a high vacuum. The finished product obtained is analytically pure.

Yield: 1.45 g (95% of theory) F .: 1540C (dec.) C16H30N407 x3HCl (499.94) Calc .: C 38.52 H 6.61 N 11.19 Found: 38.24 6.81 11.01 In this way, were synthesized the following compounds: a) 4-N-ß-Alanyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) -ß-alanyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (109sig) in ethanolic hydrochloric acid.

M.p .: 157 ° C (dec.) B) 4-N-f-Aminobutrvl-4 (R) -spectinomvcvlamin-trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) -γ-aminobutyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1720C (dec.) C) 4-N-Isoseryl-4 (R) -spectinomycylamine trihydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) isoseryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanol Hydrochloric acid.

M.p .: 114-118 ° C (dec.) D) 4-N- (4'-amino-2'-hydroxy) butyryl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (4'-benzyloxycarbonylamino-2'-hydroxy) butyryl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic acid.

F .: 134-136 ° C (dec.) E) 4-N- (N'-acetyl) glycyl-4 (R) -spectinomycylamine dihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N'-acetyl ) glycyl-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 150 ° C (dec.) F) 4-N- (N§-Methyl-N'-acetyl) glycyl-4 (R) -spectinomycylamine dihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N'-methyl-N'-acetyl) glycyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 122-128 ° C (dec.) G) 4-N-eM'-benzoyl) glycyl-4 (R) -spectinomycylamine dihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N "-benzoyl) glycyl-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 174 ° C (dec.) H) 4-N- (N'-Ethylcarbamoyl) isoseryl-4 (R) -spectinomycylamine dihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N'-ethylcarbamoyl) isoseryl-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 162-1650C (dec.) I) 4-N-D-Alanyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) -D-alany-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 147-1500C (dec.) j) 4-N- (2'-amino) valeryl-4 (R) -spectrinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (2'-benzyloxycarbonylamino) valeryl-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid F .: 150-152 C (dec.) K) 4-N- (3'-phenyl) -β-alanyl-4 (R) -spectinomycvlamine trihydrochloride Reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzylOxyCarbonyl-3g-phenyl) -β-alanyl-4 (R) -spectinomyCylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 160-162 ° C (dec.) L) 4-N- (m, m'-dichloro-p-amino) phenylglycyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6, 8-Bi-s-benzyloxycarbonyl-4-N- (N'-benzylOxycarbonyl-m, m'-dichloro-p-amino) phenylglyCyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanol Hydrochloric acid.

M.p .: 132-133 ° C (dec.) M) 4-N-D-Seryl-4 (R) -spectrinomycylamine trihydrochloride by reduction of 6,8-ice-benzyloxycarbonyl-4-N- (N'-benzyloxycarbonyl) -D-seryl-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 139-1400C (dec.) n) 4-N- (N'-methyl) -β-alanyl-4 (R) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N'-benzyloxyCarbonyl-N'-methyl) -B-alanyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 141 ° C (dec.) O) 4-N- (N'-dimethyl) -β-alanyl-4 (R) -spectrinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (N2-dimethyl) -β-alanyl-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

M.p .: 153 ° C (dec.) P) 4-N- (β-pyrrolidino) propionyl-4fR) -spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (ßpyrrolidino) propionyl-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

Q .: 148-150 C (dec.) Q) 4-N- (β- [4'-Benzylpiperidino]) propionyl-4 (R) -spectrinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (β- [4'-benzylpiperidino /) propionyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (1096ig) in ethanolic hydrochloric acid.

F .: 164-1660C (dec.) r) 4-N- (β-morpholino) propionyl-4 (-spectinomycylamine trihydrochloride by reduction of 6,8-bis-benzyloxycarbonyl-4-N- (ßmorpholino) propionyl-4 (R) -spectrinomycylamine with hydrogen and palladium-carbon (1096ig) in ethanolic hydrochloric acid.

M.p .: 127 ° C (dec.) 4-N- (β- [4'-methyl-piperidino]) propionyl-4 (R) -spectrinomycylamine-tetrahydrochloride by reducing 6,8-bis-benzyloxycarbonyl-4 - (ß- / 4'-methyl-piperazine o7) propionyl-4 (R) -spectinomycylamine with hydrogen and palladium-carbon (10%) in ethanolic hydrochloric acid.

F .: 1150C (dec.) Example 3 4-N- (5-Amino) valeryl-4 (R) -spectinomycylamine trihydrochloride 1.0 g (0.0014 mol) 6,8-bis-benzyloxycarbonyl-4-N- (4-cyano) -butyryl-4 (R) -spectinomycylamine, dissolved in 20 ml of 3% ethanolic hydrochloric acid in the presence of 1.0 g of palladium-carbon (1096ig) hydrogenated with hydrogen for 12 hours at room temperature under normal pressure.

The catalyst is separated off and the solvent is evaporated off in vacuo and dries the solid substance in a high vacuum.

Yield: 0.7 g (92% of theory) F .: 180 ° C (decomp.) C19H36N407 x3HCl (541.93) Calc .: C 42.11 H 7.25 N 10.34 Found: 42.23 7.36 10.47 example 4 4-N- (3- [N'-methyl-N'-dodecyl] -aminocarbonyl) propionyl-4 (R) -spectinomycylamine- d ihydrochloride 2.0 g 6,8-bis (4-methoxy) benzyloxyearbonyl-4-N- (3-CN'-methyl-D-dodecyl / -aminocarbonyl) propionyl-4 (R) -spectinomycylamine is dissolved in 10 ml of dioxane and, while cooling with ice, 15 ml of 4N hydrogen chloride in dioxane admitted. After 30 minutes at room temperature, the mixture was concentrated and taken up in ethanol and ether added to the point of opacity. 1.4 g of colorless powder are obtained.

F .: 120-125 ° C. Mass spectrum of the silylated compound: 830 = 614 + 3x72 902 = 614 '+ 4x72 974 = 614 + 5x72 1046 = 614 + 6x72 calculated molecular weight of the free base: 614 (C31H58N408) The following were prepared in the same way: a) 1,4-bis- / 4 (R) -spectinomycyl- (4) -aminocarbonyl / butane-tetrahydrochloride from 1,4-bis- [6,8-bis- (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomycyl- (4) -aminocarbonyl] -butane and hydrogen chloride in dioxane.

M.p .: 175-180 ° C (dec.) B) 1,7-bis- [4 (R) -spectinomycyl- (4) -aminocarbonyl] -3-oxo-4-azaheptane-tetrahydrochloride the end 1,? - bis- / 6,8-bis- (4-methoxy) benzloxycarbonyl-4 (R) -spectinomycyl- (4) -aminocarbonyl] -3-oxo-4-aza-heptane and hydrogen chloride in dioxane.

M.p .: 190-192 ° C (dec.) C) 4-N- (5-Benzoyl) valeroyl-4 (R) -spectinomycylamine dihydrochloride from 4-N-t5-benzoyl) valeroyl-6,8-bis (4-methoxy) benzyloxycarbonyl-4 (R) -spectinomycylamine and hydrogen chloride in dioxane.

M.p .: 145-155 ° C (dec.) D) 4-N- (4-n-Hexylaminocarbonyl) benzoyl-4 (R) -spectinomycylamine dihydrochloride from 4-N- (4-n-hexylaminocarbonyl) benzoyl-6,8-bis (4-methoxy) -benzyloxycarbonyl-4 (R) -spectinomycylamine and hydrogen chloride in dioxane.

M.p .: 175-180 ° C (dec.) E) 4-N- [4- (aminocarbonyl) -methylaminocarbonyl] butyryl-4 (R) -spectinomycylamine dihydrochloride from 4-N- / 4- (aminocarbonyl) -methylaminocarbonyl / butvryl-6,8-bis- (4-rethoxy) benzyloxycarbonyl-4 (R) -spectinomycylamine and hydrogen chloride in dioxane.

Q .: 160-1650C (dec.) F) 4-N- [4- (N'-methylpiperazinocarbonyl) butyryl] -4 (R) -spectinorrycvlamine dihydrochloride from 4-N- / 4 (N'-methylpiperazinocarbonyl) butyryl / -6,8-bis (4-methoxy) -benzyloxycarbonyl-4 (R) -spectinomycylamine and hydrogen chloride in dioxane.

F .: 160-165 ° C (dec.) g) 4-N- (2-Oxo) -n-propyl-4 (R) -spectinomycylamine trihydrochloride from 6t8-bis (4-methoxy) -benzyloxycarbonyl-4-N- (2-oxo) -npropyl-4 (R) -spectinomycylamine and hydrogen chloride in dioxane.

F .: 174-1760C (dec.) H) 4-N- (4-chloro) phenacyl-4 (R) -spectinomycylamine trihydrochloride from 4-N- (4-chloro) phenacyl-6,8-bis (4-metho = .y) -benzyl-oxycarbonyl-4 (R) -spectinomycylamine and hydrogen chloride in dioxane.

M.p .: 165-170 ° C (dec.) I) 4-N- (3,5-dibromo-4-amino) phenacyl-4 (R) -spectinom.ycycylamine trichloride from 4-N- (3,5-dibromo-4-amino) phenacyl-6,8-bis (4-methOxy) -benzyloxycarbonyl-4 (R) -spectinomycylamine and hydrogen chloride in dioxane.

Rf .: 0.79 (silica gel, chloroform / methanol / ammonia = 20/20/3).

The new compounds of general formula I can be used for pharmaceutical purposes Incorporate application into the usual pharmaceutical preparation forms.

The examples below describe the manufacture of some pharmaceutical products Forms of preparation: Example I Dry ampoules containing 1 g of 4-D3-ethyl-4 (R) -spectinomycylamine trihydrochloride Composition: 1 dry ampoule contains: active substance 1000.0 mg, the solvent ampoule 5 ml aqua per injection and 200 mg table salt.

Manufacturing process: A lyophilizable is placed in the dry ampoule Solution of the active ingredient poured into water, freeze-dried and closed keiia-free. The solvent is adjusted isotonic with common salt and sterile in the ampoule bottled and sterilized. Use the contents of the dry ampoule with dissolved in the solvent and injected.

Example II Ampoule with 1 g of 4-N-Isopropyl-4 (R) -spectinomycylamine trihydrochloride Composition: 1 ampoule contains: 1 g active ingredient, 200 mg table salt, aqua per inj. ad 5 ml.

Table salt and active substance are dissolved in the water, the solution is sterile-filtered and filled into ampoules under aseptic conditions.

Example III Capsules containing 0.5 g of 4-N-propyl-4 (R) -spectinomycylamine trihydrochloride 1 kg of active substance are filled into hard gelatine capsules in the usual way, in such a way that that each capsule contains 0.5 g of the active ingredient.

Example IV Dragees with 0.2 g of 4-N-isopropyl-4 (R) -spectinomycylamine trihydrochloride A mixture consisting of 1 kg of active ingredient, 2.5 kg of lactose, 0.9 kg of potato starch, 0.05 kg of magnesium stearate and 0.05 kg of talc is converted into dragee cores in the usual way pressed so that each core contains 0.2 g of active ingredient. Then the Kernels in the usual way with a coating consisting of sugar, potato starch, Talc and tragacanth coated.

Claims (10)

P atent claims 1) New Spectinomycylamine of the general formula in which R1 is a straight-chain or branched alkyl group with 1 to 18 carbon atoms, the benzyl group, the mono-, di- or tri-methylbenzyl group, the mono-, di- or trichlorobenzyl group, an acetylaminobenzyl group, the mono-, di- or tri-hydroxybenzyl group , a dimethylaminobenzyl group, the mono-, di- or tri-methoxybenzyl group, the methylenedioxybenzyl group, the cyclohexyl group; a group of the general formula II, in which R3 represents a straight-chain or branched alkyl group having 1 to 8 carbon atoms; a group of the general formula III, in which R4 represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms or the phenyl group; a group of the general formula IV, in which R5 is the methyl group, a chlorophenyl group, a methoxyphenyl group, a fluorine-substituted biphenyl group, the 3,5-dibromo-4-aminophenyl group, the ethoxy group, the methylamino, ethoxycarbonylmethylamino or isopropylamino group, the piperidino or hexamethyleneimino group, the N-methyl- (1-methyl-2-hydroxy-2-phenyl> ethylamino group, the anilino, N-methylanilino, a methylanilino, an ethoxyanilino, phenoxyanilino, thoxycarbonylanilino, methoxycarbonylanilino or the 3- Represents acetyl-4- (2-methoxy) ethoxyanilino group; or a group of the general formula V, in which R6 is a straight or branched alkyl group with 1 to 17 carbon atoms, the phenyl or benzyl group or a group of the general formula VI, - (CH2) n-R7 (VI) in which R7 is the free amino group, the methyl or dimethylamino group , represents the pyrrolidino, 4-benzylpiperidino, morpholino or N-methylpiperazino group and n has the numbers 1 to 4, R6 can also be a group of the general formula VII, in which m stands for the numbers 1 or 2, furthermore a group of the general formula VIII, in the R8. denotes the methyl, hydroxymethyl, propyl, benzyl or 4-amino-3,5-dichlorophenyl group, or a group of the general formula IX, in which R9 represents a hydrogen atom or the methyl group, R10 represents the acetyl, dodecyl or benzoyl group and p represents an integer from 1 to 4, but can also represent the 1-hydroxyl 2- (ethylaminocarbonyl) aminoethyl radical or a group of the general Formula X, - (CH2) q-CO-R11 (X) in which q is the numbers 2, 3 or 4 and R11 is the phenyl group, a straight-chain or branched alkylamino group with 2 to 18 carbon atoms, a dialkylamino group whose alkyl radicals 1 to 12 - Contain carbon atoms, the anilino group, the benzylamino group, the dibenzylamino group, the pyrrolidino group, the 4-benzylpiperidino group, the morpholino, thiomorpholino, N-methylpiperazino or sminocarbonyl-methylamino group, furthermore R6 can mean a group of the general formula XI, in which R12 denotes the hexyl or dodecyl radical, but finally R6 can also represent the groups of the general formulas XII and XIII have for the subject, where in these formulas Sp denotes the spectinomycyl (4) radical; and R2 represent a hydrogen atom or the methyl group and their physiologically acceptable acid addition salts with inorganic or organic acids. 2) New Spectinomycylamine of the general formula I according to claim 1, in which R1 is a straight-chain or branched alkyl group with 1 to 18 carbon atoms, the benzyl group, the mono-, di- or trimethylbenzyl group, the mono-, di- or Trichlorobenzyl group, an acetylaminobenzyl group, the mono-, di- or trihydroxybenzyl group, a dimethylaminobenzyl group, the mono-, di- or tri-methoxybenzyl group, the Methylenedioxybenzyl group or the cyclohexyl group and R2 is a hydrogen atom or represent the methyl group, and their physiologically acceptable acid addition salts with inorganic or organic acids. 3) New Spectinomycylamines of the general formula I according to claim 1, in which R1 is a group of the general formula II, in which R3 represents a straight-chain or branched alkyl group with 1 to 8 carbon atoms, or a group of the general formula III, in which R4 represents a straight-chain or branched alkyl group with 1 to 4 carbon atoms or the phenyl group, or a group of the general formula IV, in the Rg the methyl group, a chlorophenyl group, a methoxyphenyl group, a fluorine-substituted biphenyl group, the 3,5-dibromo-4-aminophenyl group, the ethoxy group, the methylamino, ethoxycarbonylmethylamino or isopropylamino group, the piperidino or hexamethyleneimino group, the benzylamino group , the N-methyl- (1-methyl-2-hydroxy-2-phenyl) -ethylamino group, the aenilino, N-methylanilino, a methylanilino, an ethoxyanilino, phenoxyanilino, ethoxycarbonylanilino, methoxycarbonylanilino or the 3 -Acetyl-4- (2-methoxy) ethoxyanilino group and R2 denotes a hydrogen atom or the methyl group, and their physiologically acceptable acid addition salts with inorganic or organic acids. 4) New Spectinomycylamines of the general formula I according to claim 1, in which R1 denotes a group of the general formula V, in which R6 represents a straight or branched alkyl group with 1 to 17 carbon atoms, the phenyl or benzyl group or a group of the general formula VI (CH2) nR7 (VI), in which R7 the free amino group, the methyl or dimethylamino group, the pyrrolidino -, 4-benzylpiperidino, morpholino or N-methylpiperazino group and n has the numbers 1 to 4, but R1 can also mean a group of the general formula V in which R6 is either a group of the general formula VII in which m are the numbers 1 or 2, or a group of the general formula VIII, wherein R8 denotes the methyl, hydroxymethyl, propyl, benzyl or 4-amino-3,5-dichlorophenyl group, or a group of the general formula IX, in which Rg is a hydrogen atom or the methyl group, R10 is the acetyl, dodecyl or benzoyl group and p is an integer from 1 to 4, or the 1-hydroxy-2- (ethylamiocarbonyl) aminoethyl group or a group of the general formula X, - (CH2) q-CO-R11 (X) in which q is the numbers 2, 3 or 4 and R11 is the phenyl group, a straight-chain or branched alkylamino group with 2 to 18 carbon atoms, a dialkylamino group whose alkyl radicals contain 1 to 12 carbon atoms, the anilino group , the benzylamino group, the dibenzylamino group, the pyrrolidino group, the 4-benzylpiperidino group, the morpholino, thiomorpholino, N-methylpiperazino or aminocarbonylmethylamino group, or a group of the general formula XI, in which R12 represents the hexyl or dodecyl radical, or else a group of the general formulas XII or XIII denotes in which Sp represents the spectinomycyl (4) radical, and R2 denotes a hydrogen atom or the methyl group and their physiologically acceptable acid addition salts with inorganic or organic acids. 5) New Spectinomycylamine of the general formula I according to claim 1, in which R1 is ethyl, isopropyl, dodecyl, octadecyl, (3-oxo) butyl -, (4-methyl-3-oxo) pentyl-, lauroyl-, palmitoyl-, (4- [dodecylamino-carbonyl]) - butyryl-, (4- [Tetradecylaminocarbonyl]) butyryl-, (4- [Dodecylamino-carbonyl]) - benzoyl-, (ß) -alanyl-, (4'-Amino-2'-hydroxy) butyryl-, # -aminobutyryl-, p-methoxyphenacyl-, / p- (4-fluoro) phenylphenacyl- or (4-amino-3,5-dibromo) phenacyl group and R2 is a hydrogen atom and their physiologically compatible acid addition salts with inorganic or organic ones Acids. 6) Process for the preparation of new spectinomycylamines of the general formula I according to claim 1 and their salts with inorganic or organic acids, characterized in that a 4-spectinomycylamine derivative of the general formula XIV the radicals Z are split off by means of catalytic hydrogenolysis in aqueous organic or organic solvents, by means of nascent hydrogen or by acidolytic cleavage in organic solvents, where in the general formula (XIV) the radicals R1 and R2 are as defined above and Z is one known from peptide chemistry, by acidolytic cleavage or by catalytic hydrogenation means protecting group, such as the benzyloxycarbonyl group, the 4-bromo or 4-nitro or 4-chlorobenzyloxycarbonyl group, the 4-methoxy or 3,4-dimethoxy or 34-methylenedioxy or 3 , 4,5-trimethyl or 4-decyloxy or 4-acetoxy or 4-ethoxy-carbonyloxy-benzyloxycarbonyl group, a saturated or unsaturated alkoxycarbonyl group with 1 to 12 carbon atoms, which is optionally replaced by a furyl (2) group, a p-tolylsulfonyl group, one or more halogen atoms, an alkoxy or alkoxyalkoxy group with 1 to 3 carbon atoms in the alkyl part and 1 to 3 carbons Substance atoms in the alkylene part can be substituted, for example the furyl (2) methoxycarbonyl, allyloxycarbonyl, 2- (p-tolylsulfonyl) ethoxycarbonyl, 2-bromoethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2- ( 2-methoxyethoxy) ethoxycarbonyl-, 3-methylpentyl- (3) -oxycarbonyl-, but especially the tert-butyloxycarbonyl group, a cycloalkyloxycarbonyl group with 5 to 12 carbon atoms, such as the cyclopentyloxycarbonyl or cyclohexyloxycarbonyl group, both of which are represented by a methyl, ethyl or tert-butyl group, the isobornyloxycarbonyl or the adamantyl (1) oxycarbonyl group, a phenyl or biphenylalkoxycarbonyl group which can be substituted in the phenyl radical by one to three methyl or methoxy groups and the alkylene group thereof, which is straight or may be branched, contains 2 to 4 carbon atoms, such as, for example, the dimethyl-3,5-dimethoxy-benzyloxycarbonyl or 2- / biphenylyl- ($) / -propyl (2) -oxycarbonyl group, the diFhenylmethoxycarbonyl group, a phenyloxycarbonyl group which can optionally be substituted by a nitro, methoxy or methyl group, a dialkylaminooxycarbonyl group such as the dimethylaminooxycarbonyl group or the piperidinooxycarbonyl group, an alkylthiocarbonyl group with other 1 to 4 carbon atoms in the alkyl radical, the benzylthiocylcarbonyl group aliphatic acyl group with 1 to 10 carbon atoms, which can optionally also be substituted by 1 to 3 halogen atoms, hydroxyl groups, acyl radicals, or by a nitro group, such as the trifluoroacetyl, acetoacetyl, 2-nitrophenoxyacetyl, -onochloroacetyl, 3- Chlorobutyroyl, 3-hydroxyisocaproyl group, furthermore Z can be a benzoyl, 2-nitrobenzoyl, 4-toluenesulfonyl, benzylsulfonyl or? -Methoxybenzenesulfonyl group or also a benzyl or trityl group, and optionally then a spectinomycylamine obtained in this way by means of inorganic or organic acids in its acid addition ssalz is transferred. 7) Method according to claim 6, characterized in that for the catalytic hydrogenolysis as solvents alcohols, acetic acid or dimethylformamide is used and the reaction in the presence of noble metal catalysts, such as valladium or platinum catalysts. 8) The method according to claim 6, characterized in that the acidolytic Cleavage with a hydrohalic acid, with acetic acid, trifluoroacetic acid, or with an organic sulfonic acid in glacial acetic acid, chloroform or dioxane at temperatures is carried out between 20 and 50 ° C. 9) Medicines containing one or more compounds of the general Formula I according to Claims 1 to 5 in addition to the customary carriers and / or auxiliaries. 10) Use of compounds of general formula I according to the Claims 1 to 5 for combating diseases of the respiratory tract and the pharynx, to combat otitis, pharyngitis, pneumonia, peritonitis, pyelonephritis, Cystitis, endocarditis, systemic infections, bronchitis, arthritis and local infections.