【结 构 式】 |
【分子编号】13615 【品名】(3aR,4R,5R,6aS)-4-[2-(2-Heptyl-1,3-dioxolan-2-yl)ethyl]hexahydro-2H-cyclopenta[b]furan-2,5-diol 【CA登记号】 |
【 分 子 式 】C19H34O5 【 分 子 量 】342.47596 【元素组成】C 66.64% H 10.01% O 23.36% |
合成路线1
该中间体在本合成路线中的序号:(IX)The condensation of dimethyl methylphosphonate (I) with ethyl octanoate (II) by means of butyllithium in THF gives dimethyl 2-oxononylphosphonate (III), which is condensed with the protected aldehyde (IV) by means of NaH in THF, yielding the unsaturated ketone (V). The hydrogenation of (V) with H2 over Pd/C in ethyl acetate affords the corresponding saturated ketone (VI), which is treated with ethylene glycol and p-toluenesulfonic acid to give the cyclic ketal (VII). The mild hydrolysis of (VII) with K2CO3 and acetic acid gives the alcohol derivative (VIII); the reduction of the lactone group of (VIII) with dibutylaluminum hydride in toluene affords the lactol (IX), which is condensed with (4-carboxybutyl)triphenylphosphonium bromide (X) by means of NaH in DMSO yielding the protected prostaglandin (XI). Esterification of (XI) with isopropyl iodide and DBU in acetonitrile gives the precursor (XII), which is finally deprotected with acetic acid in THF - water.
【1】 Ueno, R.; Ueno, R.; Oda, T. (Ueno Fine Chemicals Industry, Ltd.); Prostaglandins of the F series. EP 0289349; JP 1989151552; US 5001153; US 5106869 . |
【2】 Ueno, R.; Ueno, R.; Oda, T. (Ueno Fine Chemicals Industry, Ltd.); 13,14-Dihydro-15-keto-PGFs. GB 2225573 . |
【3】 Ueno, R.; Ueno, R.; Oda, T. (Ueno Fine Chemicals Industry, Ltd.); Ocular hypotensive agents. EP 0308135; JP 1994080571; US 5151444; US 5166178; US 5212200 . |
【4】 Prous, J.; Castaner, J.; UF-021. Drugs Fut 1992, 17, 3, 193. |
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) | 13607 | dimethyl methylphosphonate | 756-79-6 | C3H9O3P | 详情 | 详情 |
(II) | 13608 | ethyl octanoate; ethyl caprylate | 106-32-1 | C10H20O2 | 详情 | 详情 |
(III) | 13609 | dimethyl 2-oxononylphosphonate | C11H23O4P | 详情 | 详情 | |
(IV) | 13610 | (3aR,4R,5R,6aS)-2-oxo-4-(2-oxoethyl)hexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate | C22H20O5 | 详情 | 详情 | |
(V) | 13611 | (3aR,4R,5R,6aS)-2-oxo-4-[(E)-3-oxo-1-decenyl]hexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate | C30H34O5 | 详情 | 详情 | |
(VI) | 13612 | (3aR,4R,5R,6aS)-2-oxo-4-(3-oxodecyl)hexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate | C30H36O5 | 详情 | 详情 | |
(VII) | 13613 | (3aR,4R,5R,6aS)-4-[2-(2-heptyl-1,3-dioxolan-2-yl)ethyl]-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl [1,1'-biphenyl]-4-carboxylate | C32H40O6 | 详情 | 详情 | |
(VIII) | 13614 | (3aR,4R,5R,6aS)-4-[2-(2-Heptyl-1,3-dioxolan-2-yl)ethyl]-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one | C19H32O5 | 详情 | 详情 | |
(IX) | 13615 | (3aR,4R,5R,6aS)-4-[2-(2-Heptyl-1,3-dioxolan-2-yl)ethyl]hexahydro-2H-cyclopenta[b]furan-2,5-diol | C19H34O5 | 详情 | 详情 | |
(X) | 13616 | (4-Carboxybutyl)triphenylphosphonium bromide | 17814-85-6 | C23H24BrO2P | 详情 | 详情 |
(XI) | 13617 | (Z)-7-[(1R,2R,3R,5S)-2-[2-(2-Heptyl-1,3-dioxolan-2-yl)ethyl]-3,5-dihydroxycyclopentyl]-5-heptenoic acid | C24H42O6 | 详情 | 详情 | |
(XII) | 13618 | isopropyl (Z)-7-[(1R,2R,3R,5S)-2-[2-(2-heptyl-1,3-dioxolan-2-yl)ethyl]-3,5-dihydroxycyclopentyl]-5-heptenoate | C27H48O6 | 详情 | 详情 |