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【结 构 式】

【药物名称】Rofleponide

【化学名称】16alpha,17alpha-[(R)-Butylidenedioxy]-6alpha,9alpha-difluoro-11beta,21-dihydroxypregn-4-ene-3,20-dione

【CA登记号】144459-70-1

【 分 子 式 】C25H34F2O6

【 分 子 量 】468.54293

【开发单位】AstraZeneca (Originator)

【药理作用】GASTROINTESTINAL DRUGS, Inflammatory Bowel Disease, Agents for, Corticosteroids

合成路线1

This compound has been obtained by several related ways: 1. The selective reduction of 6alpha,9alpha-difluoro-16alpha-prednisolone (I) with H2 over tris(triphenylphosphine)rhodium chloride catalyst in ethanol gives 6alpha,9alpha-difluoro-11beta,16alpha,17alpha,21-tetrahydroxypregn-4-ene-3,20-dione (II), which is cyclized with butanal (III) catalyzed by HClO4 in dioxane to yield the butylidenedioxy derivative (IV) as a diastereomeric mixture. Finally, the desired (R)-diastereomer is separated by column chromatography over Sephadex LH-20. 2. By selective reduction of 16alpha,17alpha-((R)-butylidenedioxy)-6alpha,9alpha-difluoro-11beta,21-dihydroxypregna-1,4-diene-3,20-dione (V) with H2 over tris(triphenylphosphine)rhodium chloride catalyst in ethanol. 3. The selective reduction of fluocinolone acetonide (VI) with H2 over tris(triphenylphosphine)rhodium chloride catalyst in ethanol gives 6alpha,9alpha-difluoro-11beta,21-dihydroxy-16alpha,17alpha-(isopropylidenedioxy)pregen-4-ene-3,20-dione (VII), which is then treated with butanal (III) and HClO4 over SiO2 in heptane.

1 Andersson, P.; Axelsson, B.; Brattssand, R.; Thalen, A. (AstraZeneca plc); Novel steroids. JP 1994505232; US 5674861; US 5939409; WO 9213872 .
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) 47567 (6S,8S,9R,10S,11S,13S,14S,16R,17S)-6,9-difluoro-17-glycoloyl-11,16,17-trihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one C21H26F2O6 详情 详情
(II) 47568 (6S,8S,9R,10S,11S,13S,14S,16R,17S)-6,9-difluoro-17-glycoloyl-11,16,17-trihydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one C21H28F2O6 详情 详情
(III) 23694 butyraldehyde 123-72-8 C4H8O 详情 详情
(IV) 47569 (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-5-hydroxy-4a,6a-dimethyl-8-propyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one C25H34F2O6 详情 详情
(V) 47570 (4aS,4bR,5S,6aS,6bS,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-5-hydroxy-4a,6a-dimethyl-8-propyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one C25H32F2O6 详情 详情
(VI) 46292 (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one C24H30F2O6 详情 详情
(VII) 47571 (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one C24H32F2O6 详情 详情
Extended Information