【结 构 式】 |
【药物名称】TA-510 【化学名称】(±)-8alpha-(3,4-Dimethoxyphenyl)-4,4aalpha,5,7,7aalpha,8-hexahydrobenzo[1,2-b:4,5-c']difuran-4,7-dione 【CA登记号】133118-88-4 (diastereomer), 133163-96-9 (diastereomer) 【 分 子 式 】C18H16O6 【 分 子 量 】328.32462 |
【开发单位】Tanabe Seiyaku (Originator) 【药理作用】GASTROINTESTINAL DRUGS, Hepatoprotectants, Liver and Biliary Tract Disorders, Treatment of, Antiinflammatory Drugs |
合成路线1
Reaction of 3-furancarboxaldehyde (I) with potassium cyanide in the presence of tert-butyldimethylsilyl chloride and ZnI2 gave the O-silylated cyanohydrin (II). Addition of 2(5H)-furanone (III) to the lithium anion of (II), followed by addition of 3,4-dimethoxybenzaldehyde (V) to the intermediate (IV), yielded adduct (VI). Subsequent acid cyclization of (VI) by means of trifluoroacetic acid or methanesulfonic acid provided the tricyclic derivative (VII) as a diastereomeric mixture. Desilylation of (VII) with concomitant cyanide elimination using either tetrabutylammonium fluoride at low temperature or aqueous ammonium fluoride gave rise to ketone (VIII). This was then epimerized to the title compound by treatment with triethylamine in boiling toluene. Alternatively, desilylation of (VII) with tetrabutylammonium fluoride at room temperature provided directly the title diastereoisomer.
【1】 Iwasaki, T.; Sugiura, M.; Matsuoka, Y.; Matsumoto, M.; Kitamura, K. (Tanabe Seiyaku Co., Ltd.); Biphenyl derivs.. EP 0386778; JP 1990235884; US 5066669 . |
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) | 47247 | 3-Furaldehyde | 498-60-2 | C5H4O2 | 详情 | 详情 |
(II) | 47248 | 2-[[tert-butyl(dimethyl)silyl]oxy]-2-(3-furyl)acetonitrile | C12H19NO2Si | 详情 | 详情 | |
(III) | 19267 | 2(5H)-furanone;furan-2(5H)-one;2-Buten-1,4-olide | 497-23-4 | C4H4O2 | 详情 | 详情 |
(IV) | 47249 | C16H22LiNO4Si | 详情 | 详情 | ||
(V) | 18304 | 3,4-Dimethoxybenzaldehyde; Veratraldehyde | 120-14-9 | C9H10O3 | 详情 | 详情 |
(VI) | 47250 | 2-[[tert-butyl(dimethyl)silyl]oxy]-2-[4-[(3,4-dimethoxyphenyl)(hydroxy)methyl]-5-oxotetrahydro-3-furanyl]-2-(3-furyl)acetonitrile | C25H33NO7Si | 详情 | 详情 | |
(VII) | 47251 | (4S,4aR,7aR,8R)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-(3,4-dimethoxyphenyl)-7-oxo-4,4a,5,7,7a,8-hexahydrofuro[2,3-f][2]benzofuran-4-carbonitrile | C25H31NO6Si | 详情 | 详情 | |
(VIII) | 47252 | (4R,4aR,7aR,8R)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-(3,4-dimethoxyphenyl)-7-oxo-4,4a,5,7,7a,8-hexahydrofuro[2,3-f][2]benzofuran-4-carbonitrile | C25H31NO6Si | 详情 | 详情 | |
(IX) | 47253 | (4aR,7aR,8R)-8-(3,4-dimethoxyphenyl)-4a,5,7a,8-tetrahydrofuro[2,3-f][2]benzofuran-4,7-dione | C18H16O6 | 详情 | 详情 |