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【结 构 式】 
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【分子编号】50695 【品名】(3aR,4R,5R,6aS)-5-(benzoyloxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carboxylic acid 【CA登记号】 |
【 分 子 式 】C15H14O6 【 分 子 量 】290.27256 【元素组成】C 62.07% H 4.86% O 33.07% |
合成路线1
该中间体在本合成路线中的序号：(II)Commercially available Corey aldehyde benzoate (I) was oxidized to carboxylic acid (II) by Jones reagent at 0 C. Subsequent chlorination of (II) with SOCl2 afforded acid chloride (III). The crude acid chloride (III) was condensed with 3-hydroxy-4-methylthiazole-2-thione (IV) to yield the thiohydroxamate ester (V). Decarboxylation of (V) by means of tris(phenylthio)antimony in a flask open to air furnished alcohol (VI). Alkylation of alcohol (VI) with allyl bromide (VII) afforded allyl ether (VIII), which by epoxidation using m-chloroperbenzoic acid provided the epoxide (IX). Regiospecific epoxide opening with the Grignard reagent (X) gave alcohol (XI) as a diastereomeric mixture. The hydroxyl groups of (XI) were then protected as the bis-tetrahydropyranyl ether (XII) using dihydropyran and p-toluenesulfonic acid. Lactone reduction with DIBAL in toluene at -78 C gave the lactol (XIII).
| 【1】 Feng, Z.; et al.; Design and synthesis of 13-oxa prostaglandin analogs as antiglaucoma agents. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 236. |
| 【2】 Feng, Z.; Hellberg, M.R. (Alcon Laboratories, Inc.); 13-Oxa prostaglandins for the treatment of glaucoma and ocular hypertension. US 6232344; WO 9932441 . |
| 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) | 35585 | (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate | 39746-01-5 | C15H14O5 | 详情 | 详情 |
| (II) | 50695 | (3aR,4R,5R,6aS)-5-(benzoyloxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-carboxylic acid | C15H14O6 | 详情 | 详情 | |
| (III) | 50696 | (3aR,4R,5R,6aS)-4-(chlorocarbonyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate | C15H13ClO5 | 详情 | 详情 | |
| (IV) | 50697 | 3-Hydroxy-4-methyl-2(3H)thiazolethione; N-Hydroxy-4-methyl-2-thiazolethione; 2-Mercapto-4-methylthiazole 3-oxide | 49762-08-5 | C4H5NOS2 | 详情 | 详情 |
| (V) | 50698 | (3aR,4R,5R,6aS)-4-([[4-methyl-2-thioxo-1,3-thiazol-3(2H)-yl]oxy]carbonyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate | C19H17NO6S2 | 详情 | 详情 | |
| (VI) | 50699 | (3aR,4R,5R,6aS)-4-hydroxy-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate | C14H14O5 | 详情 | 详情 | |
| (VII) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (VIII) | 50700 | (3aR,4R,5R,6aS)-4-(allyloxy)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate | C17H18O5 | 详情 | 详情 | |
| (IX) | 50701 | (3aR,4R,5R,6aS)-4-(2-oxiranylmethoxy)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate | C17H18O6 | 详情 | 详情 | |
| (X) | 50702 | bromo[3-(trifluoromethyl)benzyl]magnesium | C8H6BrF3Mg | 详情 | 详情 | |
| (XI) | 50703 | (3aR,4R,5R,6aS)-5-hydroxy-4-[2-hydroxy-4-[3-(trifluoromethyl)phenyl]butoxy]hexahydro-2H-cyclopenta[b]furan-2-one | C18H21F3O5 | 详情 | 详情 | |
| (XII) | 50704 | (3aR,4R,5R,6aS)-5-(tetrahydro-2H-pyran-2-yloxy)-4-[2-(tetrahydro-2H-pyran-2-yloxy)-4-[3-(trifluoromethyl)phenyl]butoxy]hexahydro-2H-cyclopenta[b]furan-2-one | C28H37F3O7 | 详情 | 详情 | |
| (XIII) | 50705 | (3aR,4R,5R,6aS)-5-(tetrahydro-2H-pyran-2-yloxy)-4-[2-(tetrahydro-2H-pyran-2-yloxy)-4-[3-(trifluoromethyl)phenyl]butoxy]hexahydro-2H-cyclopenta[b]furan-2-ol | C28H39F3O7 | 详情 | 详情 |