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Updated: Sep 6, 2025

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Asymmetric Michael Addition in Synthesis of β-Substituted GABA Derivatives
Jianlin Han1, Jorge Escorihuela2, Santos Fustero2
1Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China.
Abstract:
γ-Aminobutyric acid (GABA) represents one of the most prolific structural units widely used in the design of modern pharmaceuticals. For example, β-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.
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