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A Novel Convergent Synthesis of the Antiglaucoma PGF(2α) Analogue Bimatoprost.
MedLine Citation:
PMID:  23381781     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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. Chirality, 2013. © 2013 Wiley Periodicals, Inc.
Authors:
Iwona Dams; Michał Chodyński; Małgorzata Krupa; Anita Pietraszek; Marta Zezula; Piotr Cmoch; Monika Kosińska; Andrzej Kutner
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-5
Journal Detail:
Title:  Chirality     Volume:  -     ISSN:  1520-636X     ISO Abbreviation:  Chirality     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8914261     Medline TA:  Chirality     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
Affiliation:
R&D Chemistry Department, Pharmaceutical Research Institute, Rydygiera 8, 01-793, Warsaw, Poland.
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