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【结 构 式】 
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【药物名称】SCH-60663 【化学名称】1-O-[4-[(2S,3R)-1-(4-Fluorophenyl)-3-[3(S)-(4-fluorophenyl)-3-hydroxypropyl]-4-oxo-2-azetidinyl]phenyl]-beta-D-glucopyranosiduronic acid 【CA登记号】190448-57-8 【 分 子 式 】C30H29F2NO9 【 分 子 量 】585.56373 |
【开发单位】Schering-Plough (Originator) 【药理作用】Atherosclerosis Therapy, CARDIOVASCULAR DRUGS, Lipoprotein Disorders, Treatment of , METABOLIC DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Cholesterol Absorption Inhibitors |
合成路线1
Protected glucuronic acid (I) was converted to trichloroacetimidate (II) by treatment with trichloroacetonitrile and Cs2CO3.
| 【1】 Yumibe, N.P.; Alton, K.B.; Van Heek, M.; Davis, H.R.; Vaccaro, W.D. (Schering Corp.); Sugar-substd. 2-azetidinones useful as hypocholesterolemic agents. EP 0877750; JP 1998512592; WO 9716455 . |
| 【2】 Yumibe, N.P.; Alton, K.B.; Vaccaro, W.D.; Davis, H.R.; Van Heek, M. (Schering Corp.); Sugar-substd. 2-azetidinones useful as hypocholesterolemic agents. US 5756470 . |
合成路线2
Diol (III) was acetylated with Ac2O in the presence of dimethylaminopyridine to yield diester (IV), which was selectively hydrolyzed to monoacetate (V) by means of methanolic guanidine. Coupling of phenol (V) with imidate (II) by means of boron trifluoride etherate furnished the protected glucuronide (VI). The ester groups of (VI) were finally hydrolyzed by treatment with triethylamine in aqueous methanol.
| 【1】 Yumibe, N.P.; Alton, K.B.; Van Heek, M.; Davis, H.R.; Vaccaro, W.D. (Schering Corp.); Sugar-substd. 2-azetidinones useful as hypocholesterolemic agents. EP 0877750; JP 1998512592; WO 9716455 . |
| 【2】 Yumibe, N.P.; Alton, K.B.; Vaccaro, W.D.; Davis, H.R.; Van Heek, M. (Schering Corp.); Sugar-substd. 2-azetidinones useful as hypocholesterolemic agents. US 5756470 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 42149 | methyl (2S,3R,4S,5R,6S)-3,4,5-tris(acetoxy)-6-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-2-carboxylate | C15H18Cl3NO10 | 详情 | 详情 | |
| (III) | 42150 | (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-2-azetidinone | C24H21F2NO3 | 详情 | 详情 | |
| (IV) | 42151 | 4-[(2S,3R)-3-[(3S)-3-(acetoxy)-3-(4-fluorophenyl)propyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]phenyl acetate | C28H25F2NO5 | 详情 | 详情 | |
| (V) | 42152 | (1S)-1-(4-fluorophenyl)-3-[(2S,3R)-1-(4-fluorophenyl)-2-(4-hydroxyphenyl)-4-oxoazetidinyl]propyl acetate | C26H23F2NO4 | 详情 | 详情 | |
| (VI) | 42153 | methyl (2S,3R,4S,5R,6S)-3,4,5-tris(acetoxy)-6-[4-[(2S,3R)-3-[(3S)-3-(acetoxy)-3-(4-fluorophenyl)propyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]phenoxy]tetrahydro-2H-pyran-2-carboxylate | C39H39F2NO13 | 详情 | 详情 |