jo0709605_si_004.pdf (2.1 MB)
Enantiomerically Pure Synthesis of β-Substituted γ-Butyrolactones: A Key Intermediate to Concise Synthesis of Pregabalin
journal contribution
posted on 2007-09-14, 00:00 authored by Taedong Ok, Aram Jeon, Joohee Lee, Jung Hak Lim, Chang Seop Hong, Hee-Seung LeeChiral β-substituted γ-butyrolactones are known to be
important intermediates for many biologically active compounds such as γ-aminobutyric acid (GABA) derivatives and
lignans. We have developed a general, convenient, and
scalable synthetic method for enantiomerically pure β-substituted γ-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-γ-aminobutyric acid),
an anticonvulsant drug for the treatment of peripheral
neuropathic pain.
History
Usage metrics
Categories
Keywords
Enantiomerically Pure SynthesisKey IntermediatederivativebicyclicConcise SynthesisdecarbethoxylationPregabalinenantiomericallyutilityacidisobutylButyrolactoneSubstitutedlactonemethodanticonvulsant drugnucleophilic cyclopropane ring openingChirallignanbutyrolactonescalablecompoundintermediateconfigurationpregabalinaminobutyricneuropathic painsynthesisGABA
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC