Asymmetric Michael Addition in Synthesis of ß-Substituted GABA Derivatives.

ABSTRACT

γ-Aminobutyric acid (GABA) represents one of the most prolific structural units widely used in the design of modern pharmaceuticals. For example, ß-substituted GABA derivatives are found in numerous neurological drugs, such as baclofen, phenibut, tolibut, pregabalin, phenylpiracetam, brivaracetam, and rolipram, to mention just a few. In this review, we critically discuss the literature data reported on the preparation of substituted GABA derivatives using the Michael addition reaction as a key synthetic transformation. Special attention is paid to asymmetric methods featuring synthetically useful stereochemical outcomes and operational simplicity.