CN1502239A - Preparation of a new class of acaricidal and insect-resistant compounds - Google Patents
Preparation of a new class of acaricidal and insect-resistant compounds Download PDFInfo
- Publication number
- CN1502239A CN1502239A CNA021532923A CN02153292A CN1502239A CN 1502239 A CN1502239 A CN 1502239A CN A021532923 A CNA021532923 A CN A021532923A CN 02153292 A CN02153292 A CN 02153292A CN 1502239 A CN1502239 A CN 1502239A
- Authority
- CN
- China
- Prior art keywords
- catalyzer
- monose
- coupled
- derivative
- bromo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title abstract description 14
- 241000238631 Hexapoda Species 0.000 title abstract 2
- 230000000895 acaricidal effect Effects 0.000 title abstract 2
- DBDJCJKVEBFXHG-UHFFFAOYSA-N L-Oleandrose Natural products COC1CC(O)OC(C)C1O DBDJCJKVEBFXHG-UHFFFAOYSA-N 0.000 claims abstract description 3
- DBDJCJKVEBFXHG-BNHYGAARSA-N Oleandrose Natural products O(C)[C@H]1[C@H](O)[C@H](C)O[C@H](O)C1 DBDJCJKVEBFXHG-BNHYGAARSA-N 0.000 claims abstract description 3
- 239000000642 acaricide Substances 0.000 claims abstract description 3
- GOYBREOSJSERKM-ACZMJKKPSA-N oleandrose Chemical compound O=CC[C@H](OC)[C@@H](O)[C@H](C)O GOYBREOSJSERKM-ACZMJKKPSA-N 0.000 claims abstract description 3
- 150000002771 monosaccharide derivatives Chemical class 0.000 claims abstract 3
- 238000000034 method Methods 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- LPQOADBMXVRBNX-UHFFFAOYSA-N ac1ldcw0 Chemical class Cl.C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3CCSC1=C32 LPQOADBMXVRBNX-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- -1 sulfo- Chemical class 0.000 claims description 7
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 claims description 5
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 claims description 5
- 239000002917 insecticide Substances 0.000 claims description 5
- PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 241000607479 Yersinia pestis Species 0.000 claims description 3
- XVKMFKAKITZUEX-UHFFFAOYSA-N [N].IC1C(=O)NC(C1)=O Chemical compound [N].IC1C(=O)NC(C1)=O XVKMFKAKITZUEX-UHFFFAOYSA-N 0.000 claims description 3
- 239000003905 agrochemical Substances 0.000 claims description 3
- 244000000053 intestinal parasite Species 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- ZJHSRWNUEOUFAZ-UHFFFAOYSA-N BrC1C(=O)NC(C1)=O.[N] Chemical compound BrC1C(=O)NC(C1)=O.[N] ZJHSRWNUEOUFAZ-UHFFFAOYSA-N 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- JZZIHCLFHIXETF-UHFFFAOYSA-N dimethylsilicon Chemical compound C[Si]C JZZIHCLFHIXETF-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000003921 oil Substances 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 claims 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical group C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 claims 1
- SRBFZHDQGSBBOR-QMKXCQHVSA-N alpha-L-arabinopyranose Chemical compound O[C@H]1CO[C@@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-QMKXCQHVSA-N 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 150000002466 imines Chemical class 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 239000005660 Abamectin Substances 0.000 abstract description 12
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 abstract 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 abstract 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 abstract 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 abstract 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 abstract 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 abstract 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 abstract 1
- 150000008267 fucoses Chemical class 0.000 abstract 1
- 229930182830 galactose Natural products 0.000 abstract 1
- 229960002442 glucosamine Drugs 0.000 abstract 1
- 239000008103 glucose Substances 0.000 abstract 1
- 239000003120 macrolide antibiotic agent Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 230000009466 transformation Effects 0.000 description 8
- 208000035126 Facies Diseases 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 238000003810 ethyl acetate extraction Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 230000002141 anti-parasite Effects 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002596 lactones Chemical class 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 description 2
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 229950008167 abamectin Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000005100 correlation spectroscopy Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002240 furans Chemical class 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 125000003147 glycosyl group Chemical group 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 229960002418 ivermectin Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000544061 Cuculus canorus Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 241001477931 Mythimna unipuncta Species 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000500437 Plutella xylostella Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- DRUIESSIVFYOMK-UHFFFAOYSA-N Trichloroacetonitrile Chemical compound ClC(Cl)(Cl)C#N DRUIESSIVFYOMK-UHFFFAOYSA-N 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RRZXIRBKKLTSOM-UHFFFAOYSA-N avermectin B1a Natural products C1=CC(C)C(C(C)CC)OC11OC(CC=C(C)C(OC2OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C2)C(C)C=CC=C2C3(C(C(=O)O4)C=C(C)C(O)C3OC2)O)CC4C1 RRZXIRBKKLTSOM-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 244000078703 ectoparasite Species 0.000 description 1
- 244000079386 endoparasite Species 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- WCYAALZQFZMMOM-UHFFFAOYSA-N methanol;sulfuric acid Chemical compound OC.OS(O)(=O)=O WCYAALZQFZMMOM-UHFFFAOYSA-N 0.000 description 1
- 230000003129 miticidal effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
本发明涉及一类新型杀螨、抗虫化合物的制备。该类化合物是具有潜在药用价值的一类大环内酯化合物，其核心是将阿维菌素(avermectins)结构上的一个夹竹桃糖(oleandrose)用化学方法置换为另一全甲基化的单糖衍生物R，即具有所示的结构通式。通式中R为全甲基化的岩藻糖(Fucose)、或树胶醛糖(Arabinose)、或半乳糖(Galactose)、或氨基葡萄糖(Glucosamine)、或葡萄糖(Glucose)。
The invention relates to the preparation of a novel acaricide and insect-resistant compound. This type of compound is a class of macrolide compounds with potential medicinal value, and its core is to replace one oleandrose on the structure of avermectins with another permethyl The monosaccharide derivative R of Li has the general structural formula as shown. In the general formula, R is fully methylated fucose, or arabinose, or galactose, or glucosamine, or glucose.
Description
Avermectin (avermectins) is one group of ten six membered ring lactone derivatives that produced by streptomycete Streptomyces avermitis, it is a kind of never poison class antibiotic agricultural chemicals of wide spectrum, be proved to be a kind of safe, efficient, low toxicity, can kill the novel anti parasite medicine of endoparasite and ectoparasite simultaneously, to domestic animal, has extremely effectively anthelmintic activity as the intestinal parasites of sheep, ox, dog, horse, pig etc.On agricultural,, be widely used on vegetables, tobacco and the flowers also as miticide and insecticide.Research in medicine also underway (Organic preparations and procedures Int., 1994,26,645-670).
Avermectins medicine has two outstanding characteristics: 1) a drug is killed nematode and external Jie's main drive thing class parasite in the body simultaneously, and expelling parasite and insecticide efficiency height are really safe and effective; 2) anti parasitic mechanism is unique, with other anti-parasite medicines do not have cross resistance (the Pesticide Science journal, 2001,3,41-45).
On structure, Avermectin is one group of glucosides that is generated by ten six membered ring lactones and a disaccharides (oleandrose), also has Spiroketals system and a hexahydrobenzene and a furans ring system that contains two six membered rings around ten six membered ring lactones.Go up the substituent different and structural difference of C22-C23 according to C5 and C25 and divide into 8 components, B1a is one of main component wherein.Evaluated biological activity shows that whole 8 natural Avermectin all are effectively to drive away domestic animal intestinal parasite medicament, but drug effect has certain difference.As agricultural chemicals, miticidal effect is higher than insecticidal effect.Wherein B1a is the most effective to pest and mite class, becomes commercialized, abamectin by name.
The structure of Avermectin
Owing to Avermectin demonstrates wide spectrum, characteristic active and be easy to degrade in environment has attracted many chemical companies input strength to study efficiently; The challenge that the complexity of structure makes numerous synthetic work persons accept to synthesize again.For further improving activity, reduce toxicity and changing its activity profile, scientists has been carried out extensive studies aspect the structure of modification of Avermectin, the transformation of carbon-to-carbon double bond (as succeeding in developing of Ivermectin HCL (ivermectin)), the transformation of hydroxyl (as the synthetic exploitation of Affirm (Merck Co.)), the transformation of side chain, the upset of chiral carbon configuration, the transformation of Spiroketals, the transformation of aglucon (lactonic ring), transformation of hexahydrobenzene and furan nucleus or the like (Organic preparations and procedures Int., 1994,26,645-670; Pure ﹠amp; Appl.Chem, 1990,62,1232-1240).The avermectin derivatives of some transformation demonstrates better biologically active, and variation has taken place for activity profile and drug resistance.The most representative as: 4 " deoxidation-4 "-epi-methylamino Avermectin B1a, to the control efficiency of tropical armyworm be 1500 times of Avermectin B1 (Experientia, 1989,45,315-316).
Studies show that the structure of modification of Avermectin can not destroy the conformation of lactonic ring, such as transformation to Spiroketals, hexahydrobenzene and furan nucleus, because of its all outside lactonic ring, little to the influence of lactonic ring conformation, so this analog derivative can keep its biologically active substantially.The present invention is based on the structure of modification of glycosyl; at first a monose acidulous water among the Avermectin B1 is taken off; C5-OH with it protects with tert-butyl group dimethyl-silicon then, connects a permethylated monose at 4 ' again, thereby produces the novel pesticide molecule of a class.
Below in conjunction with embodiment the present invention is described in detail.
Conventional method: the structure calibrating is required
1HNMR,
13CNMR,
1H-
1H COSY and
1H-
13C COSY spectrum uses Bruker ARX400 at CDCl
3In record.Chemical shift is interior mark with Me4Si, is unit representation with ppm.Mass spectrum MALTI-TOF-MS does matrix with CCA.Thin layer chromatography (TLC) is by HF
254Detect with the sulfuric acid methanol solution of 30% (v/v) UV-detector alive on the silica gel plate.Column chromatography adopts 100-200 purpose silica gel, is leacheate with ethyl acetate-benzinum.
1) glycosyl hydrolase: the commercially available abamectin Bla of 20 grams is poured in 400 milliliters of aqueous isopropanols that contain 1% concentrated sulfuric acid, and 15 degree stirred 44 hours down, neutralized with saturated solution of sodium bicarbonate, dichloromethane extraction, organic facies is concentrated into dried, common silica gel column chromatography separate compound 2, productive rate 78%.
2) protection of C5-OH: digest compound 2 with 27 and be dissolved in 120 milliliters of anhydrous dimethyl formamides; add 15.7 gram imidazoles and 15 gram tert-butyl chloro-silicanes under the room temperature; after stirring is spent the night; pour in the frozen water; use ethyl acetate extraction; organic facies is concentrated into dried, common silica gel column chromatography separate compound 3, productive rate 65%.
3) 2,3, the preparation of 4-three-oxygen-methyl isophthalic acid-ethylmercapto group-D-pectinose glycosides 4: 5 gram D-pectinoses are converted into 1-ethylmercapto group-D-pectinose glycosides (J.Org.Chem. with universal method, 1995,60,7316-7327), be dissolved under the zero degree in 60 milliliters of anhydrous dimethyl formamides, add the sodium hydride of 8 equivalents and the iodomethane of 5 equivalents, pour in the frozen water after 4 hours, use ethyl acetate extraction, organic facies is concentrated into dried, common silica gel column chromatography separate compound 4, productive rate 92%.
4) 2,3, the preparation of 4-three-oxygen-methyl isophthalic acid-ethylmercapto group-L-fucoside 5: with the same quadrat method preparation 5 of above-mentioned preparation 4, gross production rate 83%.
5) 2-'-deoxy-n; N-dimethyl-3; 4; the preparation of 6-three-oxygen-methyl isophthalic acid-ethylmercapto group-D-glucoside 7: earlier with the preparation of the method before us 3; 4; 6-three-oxy-acetyl-2-deoxidation-2-phthalimide-based-1-ethylmercapto group-D-glucoside 6 (cuckoo state; Yang Feng; Chinese patent application 01136484.x, 2001), these compound 2 grams are dissolved in the saturated methanol solution of 150 milliliters of ammonias; stirring at room 4 days; be dissolved in after the evaporated under reduced pressure in 20 milliliters of anhydrous dimethyl formamides, add the sodium hydride of 13 equivalents and the iodomethane of 8 equivalents, pour in the frozen water after 4 hours; use ethyl acetate extraction; organic facies is concentrated into dried, common silica gel column chromatography separate compound 7, productive rate 80%.
6) preparation of the permethylated monose donor 8 of 1 tribromo-acetyl imines ester: with above-mentioned 2,3,4-three-oxygen-methyl isophthalic acid-ethylmercapto group-L-fucoside 3 grams are dissolved in acetone-water (6: the 1) system, the nitrogen bromo-succinimide that adds 1.5 equivalents, after the stirring at room 2 hours, concentrating upper prop separates, its product 2.2 grams are dissolved in the anhydrous methylene chloride, the Tritox and the 2 gram Anhydrous potassium carbonates that add 3 equivalents, stirring at room 6 hours, filter, concentrate the back upper prop and separate the permethylated monose donor 8 that obtains 1 tribromo-acetyl imines ester, gross production rate 67%.
Method one:
Method two:
7) coupling reaction: method one, with 2,3,4-three-oxygen-methyl isophthalic acid-ethylmercapto group-L-fucoside 5 (75 grams, 1.2 mole) and acceptor 3 (125 restrain, 0.59 mole) be dissolved in 1 liter the N-Methyl pyrrolidone, add 4 molecular sieves, stirred 30 minutes, and under condition of nitrogen gas, added nitrogen iodo succinimide (NIS, 360 grams, 1.6 mole), continue under the room temperature to stir after 2 hours, with the reaction system suction filtration, with ethyl acetate-water extraction, use sodium thiosulfate successively, sodium bicarbonate, saturated common salt washing.Concentrate organic facies, last silica gel chromatography is separated.Leacheate is 3: 1 benzinum and an ethyl acetate.Get powdered substance 9 (119 gram) at last, productive rate 79%.Method two, under zero degree to 2,3, the mixed liquor of 4-three-oxygen-methyl-L-fucose tribromo-acetyl imines ester 8 (1 gram) and 99 (1 restrains) adds the silver trifluoromethanesulfonate of 1 equivalent, lucifuge stirring at room 10 hours, in the triethylamine and back concentrates, and last silica gel chromatography is separated, productive rate 60%.
1H?NMR：(400MHz，CDCl
3)：0.14(s，6H，-(SiCH
3)
2-)，0.89-0.95(m，19H，CH
3-28，CH
3-26a，CH
3-14a，-(CCH
3)
3，H-18a)，1.14(d，3H，CH
3-12a)，1.23-1.25(m，6H，CH
3-6
I，CH
3-6
II)1.45-1.60(m，6H，CH
3-14a，H-20a，H-16a，H-2
Ia，-CH
2-27)，1.74-1.79(m，4H，H-18e，CH
3-4a)，2.0-2.05(m，1H，H-20e)，2.23-2.30(m，4H，H-2
Ie，H-24，H-26，H-16e)，2.49-2.53(m，1H，H-12)，3.34-3.39(m，2H，H-2，H-4
I)，3.42(s，3H，OCH
3)，3.45-3.51(m，3H，H-3
I，H-3
II，H-25)，3.53，3.56，3.60(3s，9H，3?Fucose-OCH
3)，3.62-3.66(dd，1H，J
1 II，
2 II?8.1，J
3 II，
2 II?10.1Hz，H-2
II)，3.76-3.98(m，6H，H-6，H-17，H-13，H-5
I，H-4
II，H-5
II)，4.06(s，1H，7-OH)，4.43-4.44(m，1H，H-5)，4.56-4.61(dd，1H，H-8a?a-bond)，4.66-4.70(dd，1H，H-8a，e-bond)，4.73(d，1H，J
1 I，
2 I?3.4Hz，H-1
I)，4.97-5.01(m，1H，H-3)，5.31-5.36(m，2H，H-19，H-15)，5.53-5.57(dd，1H，J
23，22?2.5，J
23，24?9.9Hz，H-23)，5.60(d，1H，J
1 II，
2 II?4.0Hz，H-1
II)，5.68-5.71(m，2H，H-10，H-11)，5.74-5.78(dd，1H，H-22)，5.80-5.83(m，1H，H-9)；
13C?NMR(100MHz，CDCl
3)：-4.598，-4.870(-Si(CH
3)
2-)，12.02(C-28)，12.96(C-26a)，15.10(C-14a)，16.38(C-24a)，16.46(C-6
II)，18.42(C-6
I)，18.48(-C(CH)
3)，20.01(C-4a)，20.07(C-12a)，25.88(C-C(CH)
3)，27.48(C-27)，30.55(C-24)，34.29(C-16)，34.50(C-26)，35.17(C-2
I)，36.52(C-18)，39.70(C-12)，40.47(C-20)，45.77(C-2)，56.02(C-2
I-OCH
3)，57.98，58.57，61.68，(FUCOSE-OCH
3)，66.49(C-5
I)，66.94(C-5
II)，67.93(C-8a)，68.34(C-19)，68.41(C-6)，69.51(C-5)，74.84(C-25)，77.62(C-2
II)，79.02(C-3
I)，79.23(C-4
II)，79.26(C-4
I)，80.04(C-3
II)，80.11(C-17)，80.26(C-7)，95.31(C-1
I)，95.77(C-21)，96.95(C-1
II)，117.24(C-15)，118.37(C-3)，119.34(C-9)，124.823(C-10)，127.824(C-23)，135.34(C-14)，136.197(C-22)，137.52(C-4)，137.52(C-11)，140.18(C-8)，173.995(C-1)；MALDITIF-MS：Calcd?for?C
56H
90O
15Si，1030.6[M]；Found：1054[M+Na]
+；1070[M+K]
+.
8) deviate from protecting group: with 9 (50 milligrams; 0.049 mM) be dissolved in the mixed solvent of 1.25 milliliters of acetonitriles and 0.75 milliliter of pyridine; stirred 10 minutes; the hydrogen fluoride-pyridine solution (70%) that adds 0.75 milliliter then in the solution stirred under the reaction system room temperature after 5 hours, added 2 milliliters of ethyl acetate in reaction system; slowly add saturated sodium bicarbonate solution; layering appears in system, with 3 * 5 milliliters ethyl acetate extraction, strips.Merge organic facies, use the 1N aqueous hydrochloric acid solution successively, saturated sodium bicarbonate solution, salt washing.Drying concentrates organic facies, and last silica gel chromatography is separated.Leacheate is 1: 2 benzinum and an ethyl acetate.Get powdered substance 10 (42 milligrams), productive rate 95% at last.
1HNMR：(400MHz，CDCl
3)：0.85-0.95(m，10H，CH
3-28，CH
3-26a，CH
3-14a，H-18a)，1.14(d，3H，CH
3-12a)，1.24-1.26(m，6H，CH
3-6
I，CH
3-6
II)，1.45-1.50(m，4H，CH
3-14a，H-20a)，1.58-1.64(m，4H，H-16a，H-2
Ia，-CH
2-27)，1.76(m，1H，H-18e)，1.88(br?s，3H，CH
3-4a)，2.00-2.05(m，1H，H-20e)，2.23-2.29(m，4H，H-2
Ie，H-24，H-26，H-16e)，2.35-2.37(d，1H，J?8.3Hz，5-OH)，2.47-2.53(m，1H，H-12)，3.28-3.30(m，1H，H-2)，3.35-3.41(m，1H，H-4
I)，3.42(s，3H，OCH
3)，3.46-3.50(m，2H，H-3
II，H-25)，3.53，3.56，3.60(3s，9H，3?Fucose-OCH
3)，3.62-3.66(dd，1H，J
1 II，
2 II8.1，J
3 II，
2 II?10.1Hz，H-2
II)，3.78-4.00(m，7H，H-3
I，H-17，H-13，H-5
I，H-4
II，H-6，7-OH)，4.20-4.23(m，1H，H-5
II)，4.28-4.32(t，1H，H-5)，4.68-4.74(m，3H，2H-8a，H-1
I)，4.96(m，1H，H-3)，5.37-5.43(m，2H，H-19，H-15)，5.54-5.57(dd，1H，J
23，22?2.5，J
23，24?9.9，H-23)，5.60(d，1H，J
1 II，
2 II4.0Hz，H-1
II)，5.70-5.72(m，2H，H-10，H-11)，5.75-5.78(dd，1H，H-22)，5.85-5.88(m，1H，H-9)；
13C?NMR(100MHz，CDCl
3)：12.02(C-28)，12.96(C-26a)，15.07(C-14a)，16.38(C-24a)，16.47(C-6
II)，18.50(C-6
I)，19.97(C-4a)，20.00(C-12a)，27.50(C-27)，30.58(C-24)，34.26(C-16)，34.50(C-26)，35.17(C-2
I)，36.60(C-18)，39.83(C-12)，40.49(C-20)，45.72(C-2)，56.07(C-2
I-OCH
3)，57.99，58.87，61.70，(Fucose-OCH
3)，66.51(C-5
I)，66.97(C-5
II)，66.74(C-5)，68.15(C-19)，68.33(C-8a)，68.48(C-17)，74.89(C-25)，77.62(C-2
II)，79.02(C-3
I)，79.05(C-4
II)，79.25(C-4
I)，79.26(C-6)，80.11(C-3
II)，80.41(C-7)，82.57(C-13)，95.31(C-1
I)，95.77(C-21)，96.96(C-1
II)，118.06(C-15)，118.37(C-3)，120.43(C-9)，124.76(C-10)，127.78(C-23)，135.31(C-14)，136.298(C-22)，137.979(C-4)，138.04(C-11)，139.59(C-8)，173.72(C-1)；MALDITOF-MS：Calcd?for?C
50H
76O
15，916.52[M]；Found：939.70[M+Na]
+；955.70[M+K]
+.
9) preparation of bromo-derivative 12: at first equally prepare the triphenylphosphine of 11,1 gram 11 usefulness 3 equivalents and the bromine of 1 equivalent reacted 2 hours in ether, pour in the frozen water that contains sodium bicarbonate with preparation 8, extracted with diethyl ether, evaporate to dryness is crossed post and is got bromo-derivative 12, productive rate 81%.
10) under zero degree, add the silver trifluoromethanesulfonate of 1 equivalent to the carrene mixed liquor of bromo-derivative 12 (1 gram) and acceptor 3 (1.2 gram), lucifuge stirring at room 10 hours, in the triethylamine and back is concentrated, last silica gel chromatography separate compound 13, productive rate 69%.
11) the missible oil solution that contains 0.5% compound 10 is made into the aqueous solution of 0.02ppm, is 100% to the kill ratio of diamond-back moth.
Claims (5)
1) class novel mite, the insecticide of killing as shown in the figure, containing permethylated monose, particularly R in its structure is fucose and pectinose.
2) a kind ofly prepare above-mentioned method of killing mite, insecticide.It is characterized in that: 1, natural monose is easy to make the monosaccharide derivatives of 1 sulfo-, other methyl-etherifieds, as 5; Also can be made into the monosaccharide derivatives of 1 bromo, other methyl-etherified, as 12; Also can be made into the permethylated monose donor of 1 tribromo-acetyl imines ester, as 8.2, commercially available Avermectin B1 hydrolysis in containing the 2-propyl alcohol of 1% concentrated sulfuric acid is fallen an oleandrose and is got 2.3,25 hydroxyls with tert-butyl group dimethyl-silicon protect 3.4, be catalyzer with nitrogen iodo succinimide, sulfo-thing 5 and acceptor 3 is coupled; Or be catalyzer with the silver trifluoromethanesulfonate, bromo-derivative 12 and acceptor 3 is coupled; Or be catalyzer with the silver trifluoromethanesulfonate, tribromo-acetyl imines ester monose donor 8 and acceptor 3 is coupled, can get derivative 9 or 13.5, derivative 9 usefulness hydrogen fluoride trealment get product 10.
3) the coupled catalyzer in the claim 2 is a nitrogen iodo succinimide, nitrogen bromo-succinimide, silver trifluoromethanesulfonate.Solvent is anhydrous methylene chloride, acetonitrile, N-Methyl pyrrolidone etc.Reaction temperature is-42 to zero degree.
4) application of the compound of claim 1 in agricultural chemicals.As the missible oil solution of the above-claimed cpd of 0.5%-2% as miticide, insecticide.
5) application of the compound of claim 1 in medicine.As pest repellant as intestinal parasite.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA021532923A CN1502239A (en) | 2002-11-26 | 2002-11-26 | Preparation of a new class of acaricidal and insect-resistant compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA021532923A CN1502239A (en) | 2002-11-26 | 2002-11-26 | Preparation of a new class of acaricidal and insect-resistant compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1502239A true CN1502239A (en) | 2004-06-09 |
Family
ID=34235080
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA021532923A Pending CN1502239A (en) | 2002-11-26 | 2002-11-26 | Preparation of a new class of acaricidal and insect-resistant compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1502239A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008511564A (en) * | 2004-09-03 | 2008-04-17 | シンジェンタ パーティシペーションズ アクチェンゲゼルシャフト | Avermectin, avermectin monosaccharide and avermectin aglycone derivatives |
| CN104402953A (en) * | 2014-11-28 | 2015-03-11 | 大庆志飞生物化工有限公司 | Avermectin monosaccharide compound, as well as preparation method and application thereof |
-
2002
- 2002-11-26 CN CNA021532923A patent/CN1502239A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008511564A (en) * | 2004-09-03 | 2008-04-17 | シンジェンタ パーティシペーションズ アクチェンゲゼルシャフト | Avermectin, avermectin monosaccharide and avermectin aglycone derivatives |
| CN104402953A (en) * | 2014-11-28 | 2015-03-11 | 大庆志飞生物化工有限公司 | Avermectin monosaccharide compound, as well as preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1022284B1 (en) | Taxoid derivatives and process for producing the same | |
| DE3872939T2 (en) | METHOD FOR PRODUCING POLYESTER RESIN COMPOSITION. | |
| JP2530344B2 (en) | Reduced avermectin derivative | |
| Marquina et al. | Bioactive oleanolic acid saponins and other constituents from the roots of Viguiera decurrens | |
| JPH0130838B2 (en) | ||
| Fedina et al. | Synthesis of branched arabinofuranose pentasaccharide fragment of mycobacterial arabinans as 2-azidoethyl glycoside | |
| CA2130664C (en) | Antiparasitic agents | |
| US4609644A (en) | Epipodophyllotoxinquinone glucoside derivatives, method of production and use | |
| US6720307B2 (en) | Glycosylated analogs of fusidic acid | |
| Czernecki et al. | Synthesis of various 3'-branched 2', 3'-unsaturated pyrimidine nucleosides as potential anti-HIV agents | |
| US6143725A (en) | Glycosylated ginkgolide derivatives, their application as medicines and pharmaceutical compositions | |
| Ikeda et al. | Synthesis of neosaponins having an α-l-rhamnopyranosyl-(1→ 4)-[α-l-rhamnopyranosyl-(1→ 2)]-d-glucopyranosyl glyco-linkage | |
| CN1502239A (en) | Preparation of a new class of acaricidal and insect-resistant compounds | |
| Dellagreca et al. | Cyanogenic glycosides from Sambucus nigra | |
| DE3786562T2 (en) | 2,6-dideoxy-2-fluoro-L-talopyranose, derivatives thereof and preparation of these compounds. | |
| Çalış et al. | Antitrypanosomal cycloartane glycosides from Astragalus baibutensis | |
| Mukhopadhyay et al. | Convergent synthesis of a trisaccharide as its 2-(trimethylsilyl) ethyl glycoside related to the flavonoid triglycoside from Gymnema sylvestre | |
| Morillo et al. | Synthesis of peracetylated chacotriose | |
| EP0675895B1 (en) | Etoposide derivatives, process for their preparation, their use as a drug and in the preparation of a drug for treating cancer | |
| Cheng et al. | Synthesis of flaccidoside II, a bidesmosidic triterpene saponin isolated from Chinese folk medicine Di Wu | |
| WO2019135257A1 (en) | Artemisinic acid glycoconjugate compounds, process for preparation and use thereof | |
| US4522815A (en) | Anthracycline glycosides | |
| US9663551B2 (en) | Solanidine-derived compounds | |
| KR920001690B1 (en) | Nitrosoures derivatives process for their preparation and medicaments containing them | |
| DE69310721T2 (en) | SUGAR DERIVATIVES OF MACROLIDS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |