A novel convergent synthesis of the potent antiglaucoma agent travoprost

Autor:	Marta Zezula, Anita Pietraszek, Małgorzata Krupa, Monika Kosińska, Iwona Dams, Michał Chodyński, Piotr Cmoch, Andrzej Kutner
Rok vydání:	2013
Předmět:	chemistry.chemical_classification Nucleophilic addition Chemistry Stereochemistry Organic Chemistry Synthon Convergent synthesis Prostaglandin Biochemistry Aldehyde chemistry.chemical_compound Hydrolysis Reagent Drug Discovery medicine Travoprost medicine.drug
Zdroj:	Tetrahedron. 69:1634-1648
ISSN:	0040-4020
Popis:	The 16-(3-trifluoromethyl)phenoxy PGF2α analogue travoprost (8a) has potent topical ocular activity. A novel convergent synthesis of 13,14-en-15-ol PGF2α analogues was developed employing Julia–Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone (5Z)-(+)-15 with a new enantiomerically pure aldehyde ω-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 PGF2α 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::dc205499e51c3e1baa727864d0b05111 https://doi.org/10.1016/j.tet.2012.11.087 Zobrazit plný text záznamu Full Text from ScienceDirect