Vigabatrin (4-amino-5-hexenoic acid) is a potent and clinically approved antiepileptic agent that functions as an irreversible inhibitor of γ-aminobutyric acid aminotransferase (GABA-T), the enzyme responsible for the catabolism of the inhibitory neurotransmitter GABA in the central nervous system. Of its two enantiomers, the (S)-form is pharmacologically active, making the development of efficient, stereoselective synthetic routes to (S)-Vigabatrin of considerable importance in medicinal chemistry. This review provides a comprehensive overview of all known synthetic strategies for accessing Vigabatrin, with a primary focus on enantioselective methods for preparing the (S)-enantiomer. The article critically evaluates racemic approaches, chiral-pool strategies using amino acids and carbohydrates, asymmetric catalytic methods, modern resolution techniques, and formal synthesis. In particular, recent advancements in organocatalysis, transition-metal catalysis, and crystallization induced resolution are discussed in detail. Synthetic pathways are compared based on factors including step economy, stereoselectivity, scalability, and overall yield. This review serves as a valuable resource for researchers engaged in synthesizing GABA analogs and related neuroactive compounds, underscoring the ongoing need for improved methodologies in the asymmetric synthesis of pharmaceutical agents.
Philip et al. (Wed,) studied this question.