Premium
A Novel Convergent Synthesis of the Antiglaucoma PGF 2α Analogue Bimatoprost
Author(s) -
Dams Iwona,
Chodyński Michał,
Krupa Małgorzata,
Pietraszek Anita,
Zezula Marta,
Cmoch Piotr,
Kosińska Monika,
Kutner Andrzej
Publication year - 2013
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22123
Subject(s) - bimatoprost , chemistry , synthon , amide , stereochemistry , prostaglandin , combinatorial chemistry , glaucoma , ocular hypertension , organic chemistry , ophthalmology , biochemistry , medicine
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.