Asymmetric Organic Synthesis

Asymmetric Organic Synthesis of Non-Protenogenic Amino Acids

For a review, please see: “Total Synthesis of Natural tert-Alkylamino Hydroxy Carboxylic Acids” Kang, S. H.*; Kang, S. Y.; Lee, H. -S.*; Buglass, A. J. Chem. Rev., 2005, 105, 4537-4558.

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.

Cooperative Catalytic System

Identifying the appropriate functional groups and organizing them with correct spatial orientation on the (molecular) surface are both key steps in designing good cooperative catalysts. In order to rival enzyme catalysts, two aspects of enzymes must be considered in the catalyst design: the number of cooperating groups should be increased beyond two and chirality must be introduced to the polyfunctional catalysts.