Piriprost, U-60257
吡前列素 吡前列素钾盐 Chemical Name: 6,9-Deepoxy-6,9-(phenylimino)-DELTA6,8-prostaglandin I1; [4R-[4alpha(1E,3S*),5beta]]-1,4,5,6-Tetrahydro-5-hydroxy-4-(3-hydroxy-1-octenyl)-1-phenylcyclopenta[b]pyrrole-2-pentanoic acid
CAS No. 79672-88-1, 88851-62-1 (monoK salt)
项目整合开发状态: Phase II
项目研究机构: Pfizer (Originator)
合成路线:5epsilon-lodo-9-deoxy-6epsilon,9alpha-epoxy-PGF1alpha (I) is protected with tert-butyldimethylsilyl chloride in DMF containing imidazole yielding the disilylated compound (II),which is treated with diazabicyclononane (DBN) in DMF to give the hydroxy keto ester (III).Acetylation of (III) with acetic anhydride in pyridine affords the corresponding acetoxy compound (IV),which by hydrolysis with NaOH affords the free hydroxy acid (V).Oxidation of (V) with Jones' reagent yields the diketonic acid (VI),which by cyclization with aniline (A) in pyridine - methanol followed by esterification with diazomethane is converted into the protected ester (VII).Elimination of the silyl groups of (VII) with tetrabutylanimonium fluoride in THF gives the methyl ester of U-60,257 (VIII),which is finally hydrolyzed with NaOH in methanol.
📌 参考资料/链接：
参考文献标题:Nitrogen-containing prostacyclin analogues,their preparation and compsns.containing them
文献作者:Smith,H.W.(Pharmacia Corp.)
参考来源:EP 0029341
📄 详细内容
合成路线:5epsilon-lodo-9-deoxy-6epsilon,9alpha-epoxy-PGF1alpha (I) is protected with tert-butyldimethylsilyl chloride in DMF containing imidazole yielding the disilylated compound (II),which is treated with diazabicyclononane (DBN) in DMF to give the hydroxy keto ester (III).Acetylation of (III) with acetic anhydride in pyridine affords the corresponding acetoxy compound (IV),which by hydrolysis with NaOH affords the free hydroxy acid (V).Oxidation of (V) with Jones' reagent yields the diketonic acid (VI),which by cyclization with aniline (A) in pyridine - methanol followed by esterification with diazomethane is converted into the protected ester (VII).Elimination of the silyl groups of (VII) with tetrabutylanimonium fluoride in THF gives the methyl ester of U-60,257 (VIII),which is finally hydrolyzed with NaOH in methanol.
参考文献标题:U-60,257
文献作者:Sneddon,J.M.; Castar,J.; Serradell,M.N.; Blancafort,P.
参考来源:Drugs Fut 1983,8(10),877
产品链接: CAS No. 79672-88-1›› 产品链接: CAS No.88851-62-1››