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