Enantiomerically Pure Synthesis of β-Substituted γ-Butyrolactones: A Key Intermediate to Concise Synthesis of Pregabalin
2007-09-14T00:00:00Z (GMT) by
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 (1<i>S</i>,5<i>R</i>)- or (1<i>R</i>,5<i>S</i>)-bicyclic lactone followed by decarbethoxylation. The utility of our method was demonstrated by streamlined synthesis of pregabalin ((<i>S</i>)-3-isobutyl-γ-aminobutyric acid), an anticonvulsant drug for the treatment of peripheral neuropathic pain.