A Novel Convergent Synthesis of the Antiglaucoma PGF 2α Analogue Bimatoprost

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 (+)‐(5 Z )‐ 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 (+)‐(5 Z )‐ 15 . The preparation and identification of two synthetic impurities, 15‐ epi isomer ( 10b ) of bimatoprost and a new prostaglandin related amide (+)‐(5 Z )‐ 18 , are also described. Chirality 25:170–179, 2013 . © 2013 Wiley Periodicals, Inc.