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

Abstract

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 Introduction2 Resolution Synthetic Approaches2.1 Chemical Resolution2.2 Biocatalytic Resolution3 Asymmetric Desymmetrization3.1 Catalytic Enantioselective Desymmetrization3.2 Enzymatic Desymmetrization4 Chiral Auxiliary Induced Asymmetric Synthesis4.1 Asymmetric Michael Addition4.2 Asymmetric Aldol Addition4.3 Asymmetric Nucleophilic Substitution5 Asymmetric Reduction5.1 Catalytic Asymmetric Hydrogenation5.2 Bioreduction6 Catalytic Asymmetric Conjugate Addition7 Conclusion