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【结 构 式】 
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【分子编号】28760 【品名】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 【CA登记号】 |
【 分 子 式 】C29H28F3NO11 【 分 子 量 】623.5366696 【元素组成】C 55.86% H 4.53% F 9.14% N 2.25% O 28.23% |
合成路线1
该中间体在本合成路线中的序号：(II)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2
该中间体在本合成路线中的序号：(I)The reaction of 4'-epi-N-trifluoroacetyldaunorubicin (I) with trifluoro methanesulfonic anhydride gives the corresponding 4'-O-triflate (II), which is converted to 4'-deoxy-4'-iodo-N-trifluoroacetyldaunorubicin (III). The hydrolysis of (III) with NaOH affords 4'-deoxy-4'-iododaunorubicin (IV), which is finally brominated with Br2 and hydrolyzed with aqueous sodium formate.
| 【1】 Suarato, A.; Penco, S.; Casazza, A.M.; Arcamone, F. (Pharmacia Corp.); 4'-Iododerivatives of anthracycline glycosides. BE 0892943; DE 3214559; FR 2525225; GB 2118540; JP 58183698; US 4438105 . |
| 【2】 Suarato, A.; Penco, S.; Arcamone, F. (Pharmacia Corp.); Process for the preparation of 4'-deoxy-daunorubicin and 4'-deoxy-doxorubicin. EP 0048967; IT 1211116; US 4345070 . |
| 【3】 Castaner, R.M.; Serradell, M.N.; Nadhestani, A.N.; Castaner, J.; FCE-21954. Drugs Fut 1987, 12, 9, 849. |
| 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) | 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 | |
| (II) | 28761 | 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-iodo-2-[(trifluoromethyl)sulfonyl]tetrahydro-2H-pyran-4-yl]-2,2,2-trifluoroacetamide | C29H24F6INO12S | 详情 | 详情 | |
| (III) | 28762 | 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-iodo-2-methyltetrahydro-2H-pyran-4-yl)-2,2,2-trifluoroacetamide | C29H27F3INO10 | 详情 | 详情 | |
| (IV) | 28763 | (8S,10S)-8-acetyl-10-[[(2R,4S,5S,6S)-4-amino-5-iodo-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C27H28INO9 | 详情 | 详情 |