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

Dedicated to Dr. Nitin W. Fadnavis, Natural Products Chemistry Division, IICT, Hyderabad on the occasion of his 63rd birthday

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 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

Key words

asymmetric synthesis - total synthesis - amino acids - chiral resolution - baclofen - synthetic methods - biocatalysis

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