【结 构 式】 |
【分子编号】27364 【品名】(8S,10S)-8-glycoloyl-6,8,11-trihydroxy-10-[[(4S,5S,6S)-5-hydroxy-6-methyl-4-(4-morpholinyl)tetrahydro-2H-pyran-2-yl]oxy]-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione 【CA登记号】 |
【 分 子 式 】C31H35NO12 【 分 子 量 】613.61844 【元素组成】C 60.68% H 5.75% N 2.28% O 31.29% |
合成路线1
该中间体在本合成路线中的序号:(III)MRA-CN is a byproduct of the synthesis of 3'-deamino-3'-(4-morpholinyl)doxorubicin (III) by the reductive alkylation of doxorubicin (I) with 2,2'-oxybisacetaldehyde (II) and NaBH3CN (I). An iminium intermediate in this process evidenly undergoes nucleophilic attack by cyanide ion present in the reaction mixture, in competition with the normal attack by hydride. Unlike the expected morpholino derivative (III) (and most anthracyclines), MRA-CN is nonbasic. It remains in the organic layer (e.g., chloroform) when the morpholino derivative is extracted with dilute aqueous acid. MRA-CN is then recovered from the organic layer and purified by chromatography on silica gel using gradient elution with dichloromethane-methanol. Yields range from 15% to 40%. MRA-CN does not form an HCl salt.
【1】 Acton, E.M.; MRA-CN. Drugs Fut 1985, 10, 9, 750. |
【2】 Acton, E.M.; et al.; Intensely potent morpholinyl anthracyclines. J Med Chem 1984, 27, 5, 638-45. |
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) | 11675 | (8S,10S)-10-[[(2R,4S,5S,6S)-4-Amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-glycoloyl-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C27H29NO11 | 详情 | 详情 | |
(II) | 23126 | 2-(2-oxoethoxy)acetaldehyde;2,2'-oxydiacetaldehyde | C4H6O3 | 详情 | 详情 | |
(III) | 27364 | (8S,10S)-8-glycoloyl-6,8,11-trihydroxy-10-[[(4S,5S,6S)-5-hydroxy-6-methyl-4-(4-morpholinyl)tetrahydro-2H-pyran-2-yl]oxy]-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C31H35NO12 | 详情 | 详情 |