OSA-8302

Chemical Name: 13,14-Dihydroprostaglandin F2beta isopropyl ester; (5Z,9beta,11alpha,15S)-9,11,15-Trihydroxyprost-5-en-1-oic acid isopropyl ester
CAS No. 162478-72-0
项目整合开发状态: Preclinical
项目研究机构: Ono (Originator), Santen (Originator)
合成路线:The title compound was synthesized starting from the described intermediate (I).Hydrogenation of the olefinic double bond in the presence of PtO2 afforded (II).After protection of the free hydroxyl group of (II) as the corresponding silyl ether (III) with tert-butyldimethylsilyl chloride and imidazole,hydrolysis of the acetate ester of (III) by means of K2CO3 in MeOH furnished alcohol (IV).Further protection of (IV) employing dihydropyran and camphorsulfonic acid gave tetrahydropyranyl ether (V).Reduction of the lactone function of (V) with DIBAL in toluene at -78 C produced lactol (VI),which was submitted to a Wittig reaction with the ylide resulting from phosphonium salt (VII) and t-BuOK to yield the cis olefin (VIII).Esterification of (VIII) with isopropanol in the presence of 2-chloro-1-methylpyridinium iodide gave isopropyl ester (IX).Inversion of the configuration of the 9beta-hydroxyl group of (IX) was then achieved by Mitsunobu coupling with formic acid to give the 9beta-formate ester (X).Subsequent hydrolysis of the formate ester of (X) with K2CO3 in hot isopropanol,followed by acid deprotection of the tetrahydropyranyl and silyl groups yielded the title compound.