jo0709605_si_004.pdf (2.1 MB)

Enantiomerically Pure Synthesis of β-Substituted γ-Butyrolactones:  A Key Intermediate to Concise Synthesis of Pregabalin

Download (2.1 MB)
journal contribution
posted on 14.09.2007 by Taedong Ok, Aram Jeon, Joohee Lee, Jung Hak Lim, Chang Seop Hong, Hee-Seung Lee
Chiral 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.