A Novel Convergent Synthesis of the Antiglaucoma PGF2α Analogue Bimatoprost

ABSTRACT The 17‐phenyl PGF2α 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 prostamideF2α 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 prostamideF2α 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. Chirality 25:170–179, 2013. © 2013 Wiley Periodicals, Inc.