A novel convergent synthesis of the potent antiglaucoma agent travoprost

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• 作者：Iwona Dams^a ; ^{i.dams@ifarm.eu} ; Micha? Chody¨½ski^a ; Ma?gorzata Krupa^a ; Anita Pietraszek^a ; Marta Zezula^a ; Piotr Cmoch^a ; ^b ; Monika Kosi¨½ska^a ; Andrzej Kutner^a
• 关键词：Travoprost ; Prostaglandins ; Corey lactone ; Nucleophilic addition
• 刊名：Tetrahedron
• 出版年：2013
• 出版时间：4 February, 2013
• 年：2013
• 卷：69
• 期：5
• 页码：1634-1648
• 全文大小：836 K

文摘

The 16-(3-trifluoromethyl)phenoxy PGF_2¦Á analogue travoprost (8a) has potent topical ocular activity. A novel convergent synthesis of 13,14-en-15-ol PGF_2¦Á analogues was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone (5Z)-(+)-15 with a new enantiomerically pure aldehyde ¦Ø-chain synthon (S)-(?)-16a. Subsequent hydrolysis of protecting groups and final esterification of fluprostenol (7a) yielded travoprost (8a). The main advantages are the preparation of high purity travoprost (8a) and the application of comparatively cheap reagents. The novel convergent strategy allows the synthesis of a whole series of 13,14-en-15-ol PGF_2¦Á analogues from a common and structurally advanced prostaglandin intermediate 15. The preparation and identification of two synthetic impurities, 15-epi isomer (8b) of travoprost and a new prostaglandin related ester (5Z)-(+)-18, are also described.