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【结 构 式】

【分子编号】65205

【品名】methyl (Z)-7-[(1R,2R,3R,5S)-2-(4,4-difluoro-3-hydroxyoctyl)-5-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl]-5-heptenoate

【CA登记号】

【 分 子 式 】C26H44F2O6

【 分 子 量 】490.6285664

【元素组成】C 63.65% H 9.04% F 7.74% O 19.57%

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:(XXIV)

Oxidation of the (-)-Corey's lactone (XIV) with Collins reagent (CrO3 and pyridine) gives aldehyde (XV), which is condensed with phosphonate (IV) by means of thallium ethoxide in benzene to yield the unsaturated difluoroketolactone (XVI). Hydrogenation of compound (XVI) with H2 over Pd/C in ethyl acetate affords the saturated analogue (XVII), which is reduced with NaBH4 in methanol/THF to provide the hydroxylactone (XVIII), which is then protected at the hydroxy group with TBDMS-Cl and imidazole to give the silyl ether (XIX). Hydrolysis of the ester group of compound (XIX) in basic medium, followed by reaction with dihydropyran yields the tetrahydropyranyl ether (XX), which is reduced with DIBAL to afford the lactol (XXI). Condensation of lactol (XXI) with 4-(methoxycarbonyl)butyl triphenylphosphonium bromide (XXII) provides the unsaturated methyl ester (XXIII), which is desilylated by means of TBAF in THF to give the diol (XXIV). Finally, hydrolysis of the ester group of compound (XXIV) with NaOH in methanol yields the already described intermediate prostaglandin F2a derivative (X).

1 Ueno, R.; Ueno, R.; Kato, I.; Oda, T. (Ueno Fine Chemicals Industry, Ltd.); Prostaglandins E and anti-ulcers containing same. EP 0284180; JP 1989052753; US 5166174; US 5225439; US 5284858; US 5380709; US 5428062; US 5886034; US 6265440 .
2 Sorbera, L.A., Castaner, J., Mealy, N.E.; Lubiprostone. Drugs Fut 2004, 29 (4): 336.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IV) 65189 dimethyl 3,3-difluoro-2-oxoheptylphosphonate C9H17F2O4P 详情 详情
(X) 65194 (Z)-7-[(1R,2R,3R,5S)-2-(4,4-difluoro-3-hydroxyoctyl)-5-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl]-5-heptenoic acid C25H42F2O6 详情 详情
(XIV) 43178 (3aR,4S,5R,6aS)-4-(hydroxymethyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate 31752-99-5 C21H20O5 详情 详情
(XV) 32042 (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate C21H18O5 详情 详情
(XVI) 65198 (3aR,4R,5R,6aS)-4-[(E)-4,4-difluoro-3-oxo-1-octenyl]-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate C28H28F2O5 详情 详情
(XVII) 65199 (3aR,4R,5R,6aS)-4-(4,4-difluoro-3-oxooctyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate C28H30F2O5 详情 详情
(XVIII) 65200 (3aR,4R,5R,6aS)-4-(4,4-difluoro-3-hydroxyoctyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate C28H32F2O5 详情 详情
(XIX) 65201 (3aR,4R,5R,6aS)-4-(3-{[tert-butyl(dimethyl)silyl]oxy}-4,4-difluorooctyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate C34H46F2O5Si 详情 详情
(XX) 65202 (3aR,4R,5R,6aS)-4-(3-{[tert-butyl(dimethyl)silyl]oxy}-4,4-difluorooctyl)-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-one C26H46F2O5Si 详情 详情
(XXI) 65203 (3aR,4R,5R,6aS)-4-(3-{[tert-butyl(dimethyl)silyl]oxy}-4,4-difluorooctyl)-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-ol C26H48F2O5Si 详情 详情
(XXII) 26177 (5-methoxy-5-oxopentyl)(triphenyl)phosphonium bromide C24H26BrO2P 详情 详情
(XXIII) 65204 methyl (Z)-7-[(1R,2R,3R,5S)-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-4,4-difluorooctyl)-5-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl]-5-heptenoate C32H58F2O6Si 详情 详情
(XXIV) 65205 methyl (Z)-7-[(1R,2R,3R,5S)-2-(4,4-difluoro-3-hydroxyoctyl)-5-hydroxy-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl]-5-heptenoate C26H44F2O6 详情 详情
Extended Information