Asymmetric Synthetic Strategies of (R)-(–)-Baclofen: An Antispastic Drug

Baclofen is an antispastic drug used as a muscle relaxant in the treatment of the paroxysmal pain of trigeminal neuralgia, spasticity of the spinal cord and cerebral origin. Baclofen resides biological activity exclusively in its (R)-(–)-enantiomer. In this review, various asymmetric synthetic strategies for (R)-(–)-baclofen are described. 1 Introduction 2 Resolution Synthetic Approaches 2.1 Chemical Resolution 2.2 Biocatalytic Resolution 3 Asymmetric Desymmetrization 3.1 Catalytic Enantioselective Desymmetrization 3.2 Enzymatic Desymmetrization 4 Chiral Auxiliary Induced Asymmetric Synthesis 4.1 Asymmetric Michael Addition 4.2 Asymmetric Aldol Addition 4.3 Asymmetric Nucleophilic Substitution 5 Asymmetric Reduction 5.1 Catalytic Asymmetric Hydrogenation 5.2 Bioreduction 6 Catalytic Asymmetric Conjugate Addition 7 Conclusion