Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase
Abstract Hemiacetal compounds are valuable building blocks in synthetic chemistry, but their enzymatic synthesis is limited and often hindered by the instability of hemiacetals in aqueous environments. Here, we show that this challenge can be addressed through reaction engineering by using immobiliz...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45545-z |
| _version_ | 1797274055521337344 |
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| author | Xiaofeng Han Fuqiang Chen Huanhuan Li Ran Ge Qianqian Shen Peigao Duan Xiang Sheng Wuyuan Zhang |
| author_facet | Xiaofeng Han Fuqiang Chen Huanhuan Li Ran Ge Qianqian Shen Peigao Duan Xiang Sheng Wuyuan Zhang |
| author_sort | Xiaofeng Han |
| collection | DOAJ |
| description | Abstract Hemiacetal compounds are valuable building blocks in synthetic chemistry, but their enzymatic synthesis is limited and often hindered by the instability of hemiacetals in aqueous environments. Here, we show that this challenge can be addressed through reaction engineering by using immobilized peroxygenase from Agrocybe aegerita (AaeUPO) under neat reaction conditions, which allows for the selective C-H bond oxyfunctionalization of environmentally significant cyclic ethers to cyclic hemiacetals. A wide range of chiral cyclic hemiacetal products are prepared in >99% enantiomeric excess and 95170 turnover numbers of AaeUPO. Furthermore, by changing the reaction medium from pure organic solvent to alkaline aqueous conditions, cyclic hemiacetals are in situ transformed into lactones. Lactams are obtained under the applied conditions, albeit with low enzyme activity. These findings showcase the synthetic potential of AaeUPO and offer a practical enzymatic approach to produce chiral cyclic hemiacetals through C-H oxyfunctionalization under mild conditions. |
| first_indexed | 2024-03-07T14:52:54Z |
| format | Article |
| id | doaj.art-c9c6c26c296f4e7d9f1cb8c28d08afda |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:52:54Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj.art-c9c6c26c296f4e7d9f1cb8c28d08afda2024-03-05T19:36:13ZengNature PortfolioNature Communications2041-17232024-02-011511810.1038/s41467-024-45545-zReaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenaseXiaofeng Han0Fuqiang Chen1Huanhuan Li2Ran Ge3Qianqian Shen4Peigao Duan5Xiang Sheng6Wuyuan Zhang7College of Chemistry and Materials Science, Inner Mongolia Minzu UniversityTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesSchool of Chemical Engineering and Technology, Xi’an Jiaotong UniversityTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesTianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesAbstract Hemiacetal compounds are valuable building blocks in synthetic chemistry, but their enzymatic synthesis is limited and often hindered by the instability of hemiacetals in aqueous environments. Here, we show that this challenge can be addressed through reaction engineering by using immobilized peroxygenase from Agrocybe aegerita (AaeUPO) under neat reaction conditions, which allows for the selective C-H bond oxyfunctionalization of environmentally significant cyclic ethers to cyclic hemiacetals. A wide range of chiral cyclic hemiacetal products are prepared in >99% enantiomeric excess and 95170 turnover numbers of AaeUPO. Furthermore, by changing the reaction medium from pure organic solvent to alkaline aqueous conditions, cyclic hemiacetals are in situ transformed into lactones. Lactams are obtained under the applied conditions, albeit with low enzyme activity. These findings showcase the synthetic potential of AaeUPO and offer a practical enzymatic approach to produce chiral cyclic hemiacetals through C-H oxyfunctionalization under mild conditions.https://doi.org/10.1038/s41467-024-45545-z |
| spellingShingle | Xiaofeng Han Fuqiang Chen Huanhuan Li Ran Ge Qianqian Shen Peigao Duan Xiang Sheng Wuyuan Zhang Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase Nature Communications |
| title | Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase |
| title_full | Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase |
| title_fullStr | Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase |
| title_full_unstemmed | Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase |
| title_short | Reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase |
| title_sort | reaction engineering blocks ether cleavage for synthesizing chiral cyclic hemiacetals catalyzed by unspecific peroxygenase |
| url | https://doi.org/10.1038/s41467-024-45545-z |
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