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

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

中文翻译：

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（R）-（–）-巴氯芬的不对称合成策略：一种抗痉挛药

献给海得拉巴IICT天然产物化学部Nitin W. Fadnavis博士63岁生日之际

抽象的

巴氯芬是一种抗痉挛药物，在三叉神经痛的阵发性疼痛，脊髓痉挛和脑源性疾病的治疗中用作肌肉松弛剂。巴氯芬仅在其（R）-（-）-对映异构体中具有生物学活性。在这篇综述中，描述了（R）-（-）-baclofen的各种不对称合成策略。

1引言

2分辨率综合方法

2.1化学分辨率

2.2生物催化拆分

3不对称去对称

3.1催化对映选择性去对称化

3.2酶促不对称化

4手性辅助诱导的不对称合成

4.1不对称迈克尔加法

4.2不对称Aldol加成

4.3不对称亲核取代

5不对称还原

5.1催化不对称加氢

5.2生物还原

6催化不对称共轭加成

7结论

巴氯芬是一种抗痉挛药物，在三叉神经痛的阵发性疼痛，脊髓痉挛和脑源性疾病的治疗中用作肌肉松弛剂。巴氯芬仅在其（R）-（-）-对映异构体中具有生物学活性。在这篇综述中，描述了（R）-（-）-baclofen的各种不对称合成策略。

1引言

2分辨率综合方法

2.1化学分辨率

2.2生物催化拆分

3不对称去对称

3.1催化对映选择性去对称化

3.2酶促不对称化

4手性辅助诱导的不对称合成

4.1不对称迈克尔加法

4.2不对称Aldol加成

4.3不对称亲核取代

5不对称还原

5.1催化不对称加氢

5.2生物还原

6催化不对称共轭加成

7结论