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Unoprostone isopropyl ester, UF-021, Rescula

乌诺前列酮异丙酯Chemical Name: 15-Deoxy-20-ethyl-15-oxo-13,14-dihydroprostaglandin F2alpha isopropyl ester; 20-Ethyl-9alpha,11alpha-dihydroxy-15-oxoprost-5(Z)-enoic acid isopropyl ester; [1R-[1alpha(Z),2beta,3alpha,5alpha]]-7-[3,5-Dihydroxy-2-(3-oxodecyl)cyclopentyl]-5-heptenoic acid isopropyl ester
CAS No. 120373-24-2
项目整合开发状态: Launched-1994
项目研究机构: R-Tech Ueno (Originator), Sucampo Pharmaceuticals (Originator), Novartis Ophthalmics (Licensee), Santen (Licensee)
合成路线:This compound can be prepared by two different ways:1) The reaction of 1-benzyl-4-(hydroxymethyl)pyrrolidin-2-one (I) with SOCl2 in refluxing dichloromethane gives 1-benzyl-4-(chloromethyl)pyrrolidin-2-one (II),which is condensed with potassium phthalimide (III) in DMF yielding 1-benzyl-4-(phthalimidomethyl)pyrrolidin-2-one (IV).Finally,this compound is treated with hydrazine in ethanol and neutralized with fumaric acid.2) The dehydration of 1-benzyl-2-oxo-pyrrolidine-4-carboxamide (V) with POCl3 in hot DMF gives 1-benzyl-4-cyanopyrrolidine-2-one (VI),which is reduced with H2 and RaNi in methanol - NH3 and neutralized with fumaric acid.

合成路线: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.
📌 参考资料/链接:
参考文献标题:Prostaglandins of the F series
文献作者:Ueno,R.; Oda,T.(Ueno Fine Chemicals Industry,Ltd.)
参考来源:EP 0289349; JP 1989151552; US 5001153; US 5106869

📄 详细内容


合成路线: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.

参考文献标题:Ocular hypotensive agents
文献作者:Ueno,R.; Oda,T.(Ueno Fine Chemicals Industry,Ltd.)
参考来源:EP 0308135; JP 1994080571; US 5151444; US 5166178; US 5212200


合成路线: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.

参考文献标题:13,14-Dihydro-15-keto-PGFs
文献作者:Ueno,R.; Oda,T.(Ueno Fine Chemicals Industry,Ltd.)
参考来源:GB 2225573


合成路线: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.
参考文献标题:UF-021
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1992,17(3),193


产品链接: CAS No. 120373-24-2››