Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidines
A versatile biocatalytic desymmetric method for efficiently accessing enantiopure cis-3,4-disubstituted pyrrolidines was developed. Catalyzed by amidase-containing E. coli whole cells, a series of meso pyrrolidine-2,5-dicarboxamides were hydrolyzed to obtain 4-carbamoylpyrrolidine-3-carboxylic acid...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co. Ltd.
2021-08-01
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| Series: | Green Synthesis and Catalysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666554921000582 |
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| author | Hui-Juan Hu Qi-Qiang Wang De-Xian Wang Yu-Fei Ao |
| author_facet | Hui-Juan Hu Qi-Qiang Wang De-Xian Wang Yu-Fei Ao |
| author_sort | Hui-Juan Hu |
| collection | DOAJ |
| description | A versatile biocatalytic desymmetric method for efficiently accessing enantiopure cis-3,4-disubstituted pyrrolidines was developed. Catalyzed by amidase-containing E. coli whole cells, a series of meso pyrrolidine-2,5-dicarboxamides were hydrolyzed to obtain 4-carbamoylpyrrolidine-3-carboxylic acid derivatives in 47%–95% yields and 62% ∼ >99.5% ee values under mild condition. The catalytic efficiency and enantioselectivity are related to the substituents in the phenyl ring. The enzyme-substrate binding mode is established and the high enantioselectivity of amidase is revealed by MD simulations. The improvement of biocatalytic efficiency has been preliminarily explored through protein engineering. |
| first_indexed | 2024-12-17T12:56:25Z |
| format | Article |
| id | doaj.art-368cedd8261d452187343be47984cb26 |
| institution | Directory Open Access Journal |
| issn | 2666-5549 |
| language | English |
| last_indexed | 2024-12-17T12:56:25Z |
| publishDate | 2021-08-01 |
| publisher | KeAi Communications Co. Ltd. |
| record_format | Article |
| series | Green Synthesis and Catalysis |
| spelling | doaj.art-368cedd8261d452187343be47984cb262022-12-21T21:47:28ZengKeAi Communications Co. Ltd.Green Synthesis and Catalysis2666-55492021-08-0123324327Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidinesHui-Juan Hu0Qi-Qiang Wang1De-Xian Wang2Yu-Fei Ao3Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; State Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author. Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.A versatile biocatalytic desymmetric method for efficiently accessing enantiopure cis-3,4-disubstituted pyrrolidines was developed. Catalyzed by amidase-containing E. coli whole cells, a series of meso pyrrolidine-2,5-dicarboxamides were hydrolyzed to obtain 4-carbamoylpyrrolidine-3-carboxylic acid derivatives in 47%–95% yields and 62% ∼ >99.5% ee values under mild condition. The catalytic efficiency and enantioselectivity are related to the substituents in the phenyl ring. The enzyme-substrate binding mode is established and the high enantioselectivity of amidase is revealed by MD simulations. The improvement of biocatalytic efficiency has been preliminarily explored through protein engineering.http://www.sciencedirect.com/science/article/pii/S2666554921000582BiotransformationDesymmetrizationEnantioselectivityAmidaseCatalytic mechanism |
| spellingShingle | Hui-Juan Hu Qi-Qiang Wang De-Xian Wang Yu-Fei Ao Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidines Green Synthesis and Catalysis Biotransformation Desymmetrization Enantioselectivity Amidase Catalytic mechanism |
| title | Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidines |
| title_full | Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidines |
| title_fullStr | Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidines |
| title_full_unstemmed | Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidines |
| title_short | Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidines |
| title_sort | enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis 3 4 disubstituted pyrrolidines |
| topic | Biotransformation Desymmetrization Enantioselectivity Amidase Catalytic mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S2666554921000582 |
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