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丙二酸二甲酯对消旋硝基烯烃的立体选择性有机催化迈克尔加成反应的研究：通往4-甲基普瑞巴林核心结构的可能途径。

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure.

作者信息

Vargová Denisa, Baran Rastislav, Šebesta Radovan

机构信息

Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, SK-842 15 Bratislava, Slovakia.

出版信息

Beilstein J Org Chem. 2018 Mar 5;14:553-559. doi: 10.3762/bjoc.14.42. eCollection 2018.

DOI:10.3762/bjoc.14.42
PMID:29623117
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5852648/
Abstract

Chiral derivatives of γ-aminobutyric acid are widely used as medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er.

摘要

γ-氨基丁酸的手性衍生物作为药物被广泛使用，并且可以通过有机催化的迈克尔加成反应获得。我们在此展示了使用丙二酸二甲酯对消旋硝基烯烃进行迈克尔加成反应来立体选择性合成4-甲基普瑞巴林立体异构体。该合成的关键步骤是在手性方酰胺催化剂作用下的动力学拆分。此外，特定的有机催化剂能够以高达99:1的对映体过量提供关键迈克尔加合物的各自立体异构体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/e356f5165db2/Beilstein_J_Org_Chem-14-553-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/173bae77f71c/Beilstein_J_Org_Chem-14-553-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/6f0f7c6fae69/Beilstein_J_Org_Chem-14-553-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/49db8537f9c4/Beilstein_J_Org_Chem-14-553-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/0903d59234d4/Beilstein_J_Org_Chem-14-553-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/1c1df0aa2bb4/Beilstein_J_Org_Chem-14-553-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/e356f5165db2/Beilstein_J_Org_Chem-14-553-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/173bae77f71c/Beilstein_J_Org_Chem-14-553-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/6f0f7c6fae69/Beilstein_J_Org_Chem-14-553-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/49db8537f9c4/Beilstein_J_Org_Chem-14-553-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/0903d59234d4/Beilstein_J_Org_Chem-14-553-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/1c1df0aa2bb4/Beilstein_J_Org_Chem-14-553-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6dc/5852648/e356f5165db2/Beilstein_J_Org_Chem-14-553-g007.jpg

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本文引用的文献

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