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【结 构 式】

【分子编号】35586

【品名】(3aR,4S,5R,6aS)-4-(hydroxymethyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate

【CA登记号】

【 分 子 式 】C15H16O5

【 分 子 量 】276.28904

【元素组成】C 65.21% H 5.84% O 28.95%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(II)

Commercially available aldehyde (I) was reduced to alcohol (II) with NaBH4. After protection of the hydroxyl group of (II) as the tert-butyldiphenylsilyl ether (III), hydrolysis of the benzoate ester of (III) using K2CO3 in MeOH afforded the 11R alcohol (IV). Displacement of the hydroxyl group of (IV), with inversion of the configuration, by means of (diethylamino)sulfur trifluoride generated the 11S fluoride (V), along with minor amounts of olefin (VI). Separation was achieved by dihydroxylation of the olefin (VI) with N-methylmorpholine-N-oxide and OsO4, followed by column chromatography. Reduction of the lactone group of (V) with diisobutylaluminum hydride at -78 C yielded lactol (VIII). Wittig condensation with the phosphorane resulting from phosphonium salt (IX) and t-BuOK furnished the Z-olefin (X). The carboxylate group was then converted to isopropyl ester (XI) by treatment with isopropyl iodide and DBU.

1 Klimko, P.; Sharif, N.A.; Griffin, B.W.; Crider, J.Y.; AL-8810: A novel prostaglandin F2alpha analog with selective antagonist effects at the prostaglandin F2alpha (FP) receptor. J Pharmacol Exp Ther 1999, 290, 3, 1278.
2 Sallee, V.L.; Hellberg, M.R.; Klimko, P.G.; Zinke, P.W. (Alcon Laboratories, Inc.); 11-Halo prostaglandins for the treatment of glaucoma or ocular hypertension. WO 9820880 .
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) 35586 (3aR,4S,5R,6aS)-4-(hydroxymethyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate C15H16O5 详情 详情
(III) 35587 (3aR,4S,5R,6aS)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate C31H34O5Si 详情 详情
(IV) 35588 (3aR,4S,5R,6aS)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one C24H30O4Si 详情 详情
(V) 35589 (3aR,4S,5S,6aS)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-5-fluorohexahydro-2H-cyclopenta[b]furan-2-one C24H29FO3Si 详情 详情
(VI) 35590 (3aR,6aS)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one C24H28O3Si 详情 详情
(VII) 35591 (3aS,6aS)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4,5-dihydroxyhexahydro-2H-cyclopenta[b]furan-2-one C24H30O5Si 详情 详情
(VIII) 35592 (3aR,4S,5S,6aS)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-5-fluorohexahydro-2H-cyclopenta[b]furan-2-ol C24H31FO3Si 详情 详情
(IX) 13616 (4-Carboxybutyl)triphenylphosphonium bromide 17814-85-6 C23H24BrO2P 详情 详情
(X) 35593 (Z)-7-[(1R,2S,3S,5S)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-fluoro-5-hydroxycyclopentyl]-5-heptenoic acid C29H39FO4Si 详情 详情
(XI) 35594 isopropyl (Z)-7-[(1R,2S,3S,5S)-2-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-fluoro-5-hydroxycyclopentyl]-5-heptenoate C32H45FO4Si 详情 详情
Extended Information