Document Detail


Enantiomerically pure synthesis of beta-substituted gamma-butyrolactones: a key intermediate to concise synthesis of pregabalin.
MedLine Citation:
PMID:  17715971     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chiral beta-substituted gamma-butyrolactones are known to be important intermediates for many biologically active compounds such as gamma-aminobutyric acid (GABA) derivatives and lignans. We have developed a general, convenient, and scalable synthetic method for enantiomerically pure beta-substituted gamma-butyrolactones, with either configuration, via nucleophilic cyclopropane ring opening of (1S,5R)- or (1R,5S)-bicyclic lactone followed by decarbethoxylation. The utility of our method was demonstrated by streamlined synthesis of pregabalin ((S)-3-isobutyl-gamma-aminobutyric acid), an anticonvulsant drug for the treatment of peripheral neuropathic pain.
Authors:
Taedong Ok; Aram Jeon; Joohee Lee; Jung Hak Lim; Chang Seop Hong; Hee-Seung Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-23
Journal Detail:
Title:  The Journal of organic chemistry     Volume:  72     ISSN:  0022-3263     ISO Abbreviation:  J. Org. Chem.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-07     Completed Date:  2007-10-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985193R     Medline TA:  J Org Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7390-3     Citation Subset:  IM    
Affiliation:
Department of Chemistry and School of Molecular Science (BK21), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea 305-701.
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MeSH Terms
Descriptor/Qualifier:
4-Butyrolactone / chemical synthesis*,  chemistry
Anticonvulsants / chemical synthesis,  chemistry
Crystallography, X-Ray
Stereoisomerism
gamma-Aminobutyric Acid / analogs & derivatives*,  chemical synthesis
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0/pregabalin; 56-12-2/gamma-Aminobutyric Acid; 96-48-0/4-Butyrolactone

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