|
【结 构 式】 
|
【药物名称】Misoprostol, SC-29333, Misopess, Cytotec 【化学名称】(±)-15-Deoxy-16(RS)-hydroxy-16-methyl-PGE1 methyl ester 【CA登记号】59122-46-2 【 分 子 式 】C22H38O5 【 分 子 量 】382.54516 |
【开发单位】Pfizer (Originator), Cytokine PharmaSciences (Not Determined) 【药理作用】Antiulcer Drugs, ENDOCRINE DRUGS, GASTROINTESTINAL DRUGS, Gynecological Disorders, Treatment of , Uterine Stimulants, Uterine Stimulants and Tocolytics, Prostaglandins |
合成路线1
The sililation of 4-methyl-1-octin-4-ol (I) with trimethylsilyl chloride by means of triethylamine in DMF gives the corresponding silyloxy derivative (II), which is treated with diisobutyl aluminum hydride and I2 in toluene - THF yielding 4-methyl-(RS)-4-trimethylsilyloxy-trans-1-octene-1-yl iodide (III). The condensation of (III) with the complex of copper 1-pentynilyde and HMPT (IV) by means of butyllithium in hexane affords the complex salt (V), which, without isolation, is allowed to react with methyl 7-[3-[(RS)-tetrahydropyranyl-2-oxy]-5-oxo-1-cyclopentenyl]-heptanoate (VI) in ethyl ether to give methyl 7-[3-(tetrahydropyranyl-2-oxy)-2-(4-methyl-4-trimethylsilyloxy-trans-1-octene-1-yl)-5-oxo-cyclopentyl]heptanoate (VII). Finally, this compound is hydrolyzed with a mixture acetic acid - water - THF at room temperature.
| 【1】 Collins P.W.; et al.; Influence of the position of the side-chain hydroxy group on the biological properties of prostaglandins. Tetrahedron Lett 1975, 48, 4217-20. |
| 【2】 Pappo, R.; Collins, P.W.; 16-Oxygenated prostanoic acid derivatives. BE 0827127; DE 2513212; FR 2274289; GB 1492426; JP 50135059; US 3965143 . |
| 【3】 Castaner, J.; Hillier, K.; SC-29333. Drugs Fut 1977, 2, 12, 817. |
| 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) | 29066 | 4-methyl-1-octyn-4-ol | C9H16O | 详情 | 详情 | |
| (II) | 33906 | 1-butyl-1-methyl-3-butynyl trimethylsilyl ether; [(1-butyl-1-methyl-3-butynyl)oxy](trimethyl)silane | C12H24OSi | 详情 | 详情 | |
| (III) | 33907 | [[(E)-1-butyl-4-iodo-1-methyl-3-butenyl]oxy](trimethyl)silane; (E)-1-butyl-4-iodo-1-methyl-3-butenyl trimethylsilyl ether | C12H25IOSi | 详情 | 详情 | |
| (IV) | 29069 | 1-pentynylcopper | C5H7Cu | 详情 | 详情 | |
| (V) | 33908 | C17H32CuLiOSi | 详情 | 详情 | ||
| (VI) | 33909 | methyl 7-[(1R,4S)-2-oxo-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]heptanoate | C19H32O5 | 详情 | 详情 | |
| (VII) | 33910 | methyl 7-[(1R,2S,3R)-2-[(E)-4-methyl-4-[(trimethylsilyl)oxy]-1-octenyl]-5-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]heptanoate | C31H56O6Si | 详情 | 详情 |