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【结 构 式】 
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【药物名称】Ladirubicin, PNU-159548, FCE-28729 【化学名称】3'-(1-Aziridinyl)-3'-deamino-4-demethoxy-4'-O-(methanesulfonyl)daunomycin 【CA登记号】171047-47-5 【 分 子 式 】C29H31NO11S 【 分 子 量 】601.63452 |
【开发单位】Pfizer (Originator) 【药理作用】Antibiotics and Alkaloids, Antineoplastic Antibiotics, Oncolytic Drugs, Anthracyclines |
合成路线1
Alkylation of 4-(demethoxy)daunorubicin (I) with 2-bromoethanol (II) affords the hydroxyethyl amine (III). This is treated with methanesulfonyl chloride and diisopropyl ethylamine to produce the bis-mesylate (IV). Cyclization of (IV) to the title aziridino derivative is then accomplished by treatment with silicagel or with diisopropyl ethylamine.
| 【1】 Fontana, E.; Felicini, C.; Synthesis of PNU-159548 labelled with 14C and 2H. J Label Compd Radiopharm 2002, 45, 7, 543. |
| 【2】 Bargiotti, A.; Caruso, M.; Grandi, M.; Ripamonti, M.; Suarato, A. (Pharmacia AB); 3'-Aziridino-anthracycline derivs.. EP 0683788; JP 1996506835; US 5532218; WO 9516695 . |
| 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) | 57492 | (7S,9S)-9-acetyl-7-{[(4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-6,9,11-trihydroxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C26H27NO9 | 详情 | 详情 | |
| (II) | 10059 | Ethylene bromohydrin; 2-Bromo-1-ethanol | 540-51-2 | C2H5BrO | 详情 | 详情 |
| (III) | 57493 | (7S,9S)-9-acetyl-6,9,11-trihydroxy-7-({(4S,5S,6S)-5-hydroxy-4-[(2-hydroxyethyl)amino]-6-methyltetrahydro-2H-pyran-2-yl}oxy)-7,8,9,10-tetrahydro-5,12-naphthacenedione | C28H31NO10 | 详情 | 详情 | |
| (IV) | 57494 | (2S,3S,4S)-6-{[(1S,3S)-3-acetyl-3,5,12-trihydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy}-2-methyl-4-({2-[(methylsulfonyl)oxy]ethyl}amino)tetrahydro-2H-pyran-3-yl methanesulfonate | C30H35NO14S2 | 详情 | 详情 |
合成路线2
The title aziridine derivative was prepared by treatment of the known 4-demethoxy-N-(2-hydroxyethyl)-4'-O-metanesulfonyldaunorubicin (I) with silica gel in a dichloromethane/methanol solution.
| 【1】 Bargiotti, A.; Caruso, M.; Grandi, M.; Ripamonti, M.; Suarato, A. (Pharmacia AB); 3'-Aziridino-anthracycline derivs.. EP 0683788; JP 1996506835; US 5532218; WO 9516695 . |
| 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) | 58757 | (2S,3S,4S,6R)-6-{[(1S,3S)-3-acetyl-3,5,12-trihydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy}-4-[(2-hydroxyethyl)amino]-2-methyltetrahydro-2H-pyran-3-yl methanesulfonate | C29H33NO12S | 详情 | 详情 |