Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanediones
Chiral 3-hydroxycyclohexane-1-ones are widely used as building blocks in the synthesis of natural products and bioactive compounds, and preparation of their single stereoisomers is still quite challenging. Through screening the available carbonyl reductases, two enzymes were found to catalyze the de...
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| Format: | Article |
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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/S2666554921000405 |
| _version_ | 1819122023287226368 |
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| author | Liangyan Zhu Yunfeng Cui Xi Chen Hongliu Zhang Jinhui Feng Qiaqing Wu Dunming Zhu |
| author_facet | Liangyan Zhu Yunfeng Cui Xi Chen Hongliu Zhang Jinhui Feng Qiaqing Wu Dunming Zhu |
| author_sort | Liangyan Zhu |
| collection | DOAJ |
| description | Chiral 3-hydroxycyclohexane-1-ones are widely used as building blocks in the synthesis of natural products and bioactive compounds, and preparation of their single stereoisomers is still quite challenging. Through screening the available carbonyl reductases, two enzymes were found to catalyze the desymmetric reduction of 2-benzyl-2-methyl-1,3-cylcohexanedione analogues to give the corresponding (2R,3R) or (2S,3S) 3-hydroxycyclohexane-1-ones bearing an all-carbon chiral quaternary center with excellent enantioselectivity (up to >99% ee) and diastereoselectivity (up to >99:1 dr). These results demonstrated the carbonyl reductases as powerful catalysts for the desymmetric reduction of 1,3-cylcohexanediones, although further studies are required to search for more enzymes to expand the substrate scope and stereopreference. |
| first_indexed | 2024-12-22T06:45:51Z |
| format | Article |
| id | doaj.art-1f399f8111134481be81d0bb58de9a62 |
| institution | Directory Open Access Journal |
| issn | 2666-5549 |
| language | English |
| last_indexed | 2024-12-22T06:45:51Z |
| publishDate | 2021-08-01 |
| publisher | KeAi Communications Co. Ltd. |
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| series | Green Synthesis and Catalysis |
| spelling | doaj.art-1f399f8111134481be81d0bb58de9a622022-12-21T18:35:16ZengKeAi Communications Co. Ltd.Green Synthesis and Catalysis2666-55492021-08-0123320323Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanedionesLiangyan Zhu0Yunfeng Cui1Xi Chen2Hongliu Zhang3Jinhui Feng4Qiaqing Wu5Dunming Zhu6National Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaNational Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, ChinaNational Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors. National Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, China.National Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, ChinaNational Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaNational Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors. National Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, China.National Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Research Center of Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and National Innovation Center for Synthetic Biotechnology, Tianjin 300308, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaChiral 3-hydroxycyclohexane-1-ones are widely used as building blocks in the synthesis of natural products and bioactive compounds, and preparation of their single stereoisomers is still quite challenging. Through screening the available carbonyl reductases, two enzymes were found to catalyze the desymmetric reduction of 2-benzyl-2-methyl-1,3-cylcohexanedione analogues to give the corresponding (2R,3R) or (2S,3S) 3-hydroxycyclohexane-1-ones bearing an all-carbon chiral quaternary center with excellent enantioselectivity (up to >99% ee) and diastereoselectivity (up to >99:1 dr). These results demonstrated the carbonyl reductases as powerful catalysts for the desymmetric reduction of 1,3-cylcohexanediones, although further studies are required to search for more enzymes to expand the substrate scope and stereopreference.http://www.sciencedirect.com/science/article/pii/S26665549210004052,2-Disubstituted 1,3-cyclohexanedioneDesymmetric reductionCarbonyl reductaseChiral cyclic 3-hydroxy ketoneBiocatalysis |
| spellingShingle | Liangyan Zhu Yunfeng Cui Xi Chen Hongliu Zhang Jinhui Feng Qiaqing Wu Dunming Zhu Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanediones Green Synthesis and Catalysis 2,2-Disubstituted 1,3-cyclohexanedione Desymmetric reduction Carbonyl reductase Chiral cyclic 3-hydroxy ketone Biocatalysis |
| title | Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanediones |
| title_full | Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanediones |
| title_fullStr | Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanediones |
| title_full_unstemmed | Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanediones |
| title_short | Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanediones |
| title_sort | synthesis of single stereoisomers of 2 2 disubstituted 3 hydroxycyclohexane 1 ones via enzymatic desymmetric reduction of the 1 3 cyclohexanediones |
| topic | 2,2-Disubstituted 1,3-cyclohexanedione Desymmetric reduction Carbonyl reductase Chiral cyclic 3-hydroxy ketone Biocatalysis |
| url | http://www.sciencedirect.com/science/article/pii/S2666554921000405 |
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