title: A novel convergent synthesis of the antiglaucoma PGF2α analogue bimatoprost.
abstract: The 17-phenyl PGF(2α) analogue bimatoprost (10a) is the most efficacious ocular hypotensive agent currently available for the treatment of glaucoma or ocular hypertension. A novel convergent synthesis of 13,14-en-15-ol prostamideF(2α) analogues was developed employing Julia-Lythgoe olefination of the structurally advanced phenylsulfone (+)-(5Z)-15 with an enantiomerically pure aldehyde ω-chain synthon (-)-(S)-16a. Subsequent hydrolysis of protecting groups and final amidation of the diol 26a yielded bimatoprost (10a). The main advantage of the current strategy is the preparation of high-purity bimatoprost (10a). The novel convergent strategy allows the synthesis of a whole series of 13,14-en-15-ol prostamideF(2α) analogues with the desired C-15 asymmetric center configuration from a common and structurally advanced prostaglandin intermediate (+)-(5Z)-15. The preparation and identification of two synthetic impurities, 15-epi isomer (10b) of bimatoprost and a new prostaglandin related amide (+)-(5Z)-18, are also described.
authors: R&D Chemistry Department, Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland. i.dams@ifarm.eu
authors: Iwona
authors: I
authors: Dams
authors: Michał
authors: M
authors: Chodyński
authors: Małgorzata
authors: M
authors: Krupa
authors: Anita
authors: A
authors: Pietraszek
authors: Marta
authors: M
authors: Zezula
authors: Piotr
authors: P
authors: Cmoch
authors: Monika
authors: M
authors: Kosińska
authors: Andrzej
authors: A
authors: Kutner
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000069580:Bimatoprost; D003008:Cloprostenol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D005901:Glaucoma / Q000188:drug therapy; D015394:Molecular Structure
chemical_list: D000577:Amides; D003008:Cloprostenol; D015237:Dinoprost; D000069580:Bimatoprost