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【结 构 式】 
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【药物名称】Galarubicin hydrochloride, DA-125 【化学名称】14-O-(3-Aminopropionyl)-7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinone hydrochloride 【CA登记号】140637-82-7, 195612-80-7 (free base) 【 分 子 式 】C30H33ClFNO13 【 分 子 量 】670.04781 |
【开发单位】Dong-A (Originator) 【药理作用】Antibiotics and Alkaloids, Antineoplastic Antibiotics, Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, Leukemia Therapy, ONCOLYTIC DRUGS, Anthracyclines |
合成路线1
Coupling of daunomycinone (III) with 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl bromide (II), which was obtained from 1,3,4-tri-O-acetyl-derivative (I), was performed by a Koenings-Knorr type of reaction to obtain the daunomycin derivative (IV). Deprotection of (IV) with sodium hydroxide in water gave corresponding derivative (V), which was subsequently treated with bromine in dichloromethane and acetone to afford the bromo derivative (VI). Condensation of (VI) with N-Boc-beta-alanine sodium salt (VII) in acetone/water gave the protected beta-alaninate derivative (VIII), which was finally treated with hydrochloride in ether to obtain DA-125.
| 【1】 Ok, D.K.; Kim, M.S.; Jung, D.Y. (Dong-A Pharmaceutical Co., Ltd.); L-Talopyranoside derivs. and process for the preparation of same. US 5374746 . |
| 【2】 Lee, M.G.; Yang, J.; DA-125. Drugs Fut 1996, 21, 8, 782. |
| 【3】 Tsuchiya, T.; Takagi, Y.; Oka, K.D.; Umezawa, S.; Takeuchi, T.; Wako, N.; Umezawa, H.; Syntheses and antitumor activities of 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)-daunomycinone and adriamycinone. J Antibiot 1986, 39, 11, 731-3. |
| 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) | 16221 | (2S,3R,4R,5R,6S)-2,5-bis(acetoxy)-3-fluoro-6-methyltetrahydro-2H-pyran-4-yl acetate | C12H17FO7 | 详情 | 详情 | |
| (II) | 16222 | (2S,3S,4R,5R,6S)-3-(acetoxy)-6-bromo-5-fluoro-2-methyltetrahydro-2H-pyran-4-yl acetate | C10H14BrFO5 | 详情 | 详情 | |
| (III) | 16223 | (8S,10S)-8-acetyl-6,8,10,11-tetrahydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | 21794-55-8 | C21H18O8 | 详情 | 详情 |
| (IV) | 16224 | (2S,3R,4R,5R,6R)-3-(acetoxy)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy]-5-fluoro-2-methyltetrahydro-2H-pyran-4-yl acetate | C31H31FO13 | 详情 | 详情 | |
| (V) | 16225 | (8S,10S)-8-acetyl-10-[[(2R,3R,4R,5S,6S)-3-fluoro-4,5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C27H27FO11 | 详情 | 详情 | |
| (VI) | 16226 | (8S,10S)-10-[[(3aR,4S,6R,7R,7aR)-7-fluoro-2,2,4-trimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]oxy]-8-(2-bromoacetyl)-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C30H30BrFO11 | 详情 | 详情 | |
| (VII) | 16227 | sodium 3-[(tert-butoxycarbonyl)amino]propanoate | C8H14NNaO4 | 详情 | 详情 | |
| (VIII) | 16228 | 2-((2S,4S)-4-[[(3aR,4S,6R,7R,7aR)-7-fluoro-2,2,4-trimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]oxy]-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-2-naphthacenyl)-2-oxoethyl 3-[(tert-butoxycarbonyl)amino]propanoate | C38H44FNO15 | 详情 | 详情 | |
| (IX) | 16229 | 2-((2S,4S)-4-[[(2R,3R,4R,5S,6S)-3-fluoro-4,5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-2-naphthacenyl)-2-oxoethyl 3-aminopropanoate | C30H32FNO13 | 详情 | 详情 |