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【结 构 式】 
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【分子编号】18698 【品名】7-(3-Amino-2,3,6-trideoxy-L-lyxo-hexosyloxy)-9-acetyl-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-naphthacenequinone; (8S,10S)-8-acetyl-10-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione; (1S,3S)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-alpha-lyxo-hexopyranoside; Daunomycin 【CA登记号】20830-81-3 |
【 分 子 式 】C27H29NO10 【 分 子 量 】527.528 【元素组成】C 61.47% H 5.54% N 2.66% O 30.33% |
合成路线1
该中间体在本合成路线中的序号：(I)The ketalization of daunorubicin (I) in the usual way gives daunorubicin-13-dimethylketal (II), which is brominated to 14-bromodaunorubicin-13-dimethylketal (III). The hydrolysis of (III) yields 14-bromodaunorubicin (IV), which is finally treated with sodium diethoxyacetate in refluxing acetone. The title product can also be obtained by reaction of (III) with sodium diethoxyacetate (A) in the same way.
| 【1】 Maral, R.; et al.; Preparation and experimental antitumor activity of a new semi-synthetic compound: 14-Diethoxy daunorubicin (RP 33921). Compt Rend Acad Sci 1978, 443-446. |
| 【2】 Blancafort, P.; Bernard, J.; Castaner, J.; Serradell, M.N.; Jacquillat, C.; Detorubicin. Drugs Fut 1981, 6, 3, 139. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 37419 | sodium 2,2-diethoxyacetate | C6H11NaO4 | 详情 | 详情 | |
| (I) | 18698 | 7-(3-Amino-2,3,6-trideoxy-L-lyxo-hexosyloxy)-9-acetyl-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-naphthacenequinone; (8S,10S)-8-acetyl-10-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione; (1S,3S)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-alpha-lyxo-hexopyranoside; Daunomycin | 20830-81-3 | C27H29NO10 | 详情 | 详情 |
| (II) | 37416 | (8S,10S)-10-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-(1,1-dimethoxyethyl)-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C29H35NO11 | 详情 | 详情 | |
| (III) | 37417 | (8S,10S)-10-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-(2-bromo-1,1-dimethoxyethyl)-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C29H34BrNO11 | 详情 | 详情 | |
| (IV) | 37418 | (8S,10S)-10-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-(2-bromoacetyl)-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C27H28BrNO10 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The reaction of daunomycin (I) with trifluoroacetic anhydride in chloroform, and boiling the reaction product with methanol gives N-trifluoroacetyldaunomycin (II), which upon treatment with iodine and calcium oxide in THF gives 14-iodo-N-trifluoroacetyldaunomycin (III). Compound (III) treated with sodium valerate (A) in boiling acetone gives the title compound. The final purification is achieved with silicic acid using chloroform-ethanol (100:1) as solvent.
| 【1】 Israel, M.; et al.; N-Trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor avtivity and less toxicity than adriamycin. Cancer Res 1975, 35, 1365-68. |
| 【2】 Israel, M.; Modest, E.J. (Sidney Farber Cancer Institute, Inc.); N-trifluoroacetyladriamycin-14-alkanoates and therapeutic compositions containing same. CA 1060003; US 4035566 . |
| 【3】 Albonico, S.M.; AD-32. Drugs Fut 1980, 5, 4, 171. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 31907 | Sodium valerate; Sodium pentanoate | C5H9NaO2 | 详情 | 详情 | |
| (I) | 18698 | 7-(3-Amino-2,3,6-trideoxy-L-lyxo-hexosyloxy)-9-acetyl-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-naphthacenequinone; (8S,10S)-8-acetyl-10-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione; (1S,3S)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-alpha-lyxo-hexopyranoside; Daunomycin | 20830-81-3 | C27H29NO10 | 详情 | 详情 |
| (II) | 28760 | N-Trifluoroacetyldaunomycin; N-((2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy]-3-hydroxy-2-methyltetrahydro-2H-pyran-4-yl)-2,2,2-trifluoroacetamide | C29H28F3NO11 | 详情 | 详情 | |
| (III) | 32677 | 14-Iodo-N-trifluoroacetyldaunomycin; 2,2,2-trifluoro-N-((2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-iodoacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy]tetrahydro-2H-pyran-4-yl)acetamide | C29H27F3INO11 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)By condensation of daunorubicin-HCl (I) with benzoylhydrazine (II) by means of acetic acid in ethanol at 60 C.
| 【1】 Jolles, G.; Neue Naphthacenderivate und ihre Herstellung. DE 2327211 . |
| 【2】 Castaner, J.; Woodman, R.J.; Zorubicin. Drugs Fut 1979, 4, 1, 61. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18698 | 7-(3-Amino-2,3,6-trideoxy-L-lyxo-hexosyloxy)-9-acetyl-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-naphthacenequinone; (8S,10S)-8-acetyl-10-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione; (1S,3S)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-alpha-lyxo-hexopyranoside; Daunomycin | 20830-81-3 | C27H29NO10 | 详情 | 详情 |
| (II) | 33310 | benzoylhydrazine; benzhydrazide; benzohydrazide | 613-94-5 | C7H8N2O | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)Condensation of two molecules of daunorubicin hydrochloride (I) with a,a'-dibromo-p-xylene (II) in the presence of Na2CO3 in DMF-CH2Cl2 at room temperature afforded the bis-daunorubicin derivative, which was purified by column chromatography and precipitated as the dihydrochloride from a MeOH-Et2O solution.
| 【1】 Priebe, W.; Chaires, J.B.; Przewloka, T.; Fokt, I.; Perez-Soler, R.; Bis-anthracyclines with high activity against doxorubicin resistant tumors. EP 0971716; JP 2000506899; WO 9734612 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18698 | 7-(3-Amino-2,3,6-trideoxy-L-lyxo-hexosyloxy)-9-acetyl-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-naphthacenequinone; (8S,10S)-8-acetyl-10-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione; (1S,3S)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-alpha-lyxo-hexopyranoside; Daunomycin | 20830-81-3 | C27H29NO10 | 详情 | 详情 |
| (II) | 18697 | 1,4-bis(bromomethyl)benzene | 623-24-5 | C8H8Br2 | 详情 | 详情 |