{"title":"通过卤代卤化酶催化螺环氧化物扩环,生物催化构建螺-噁唑烷酮类化合物","authors":"Jin-Mei Ma, Yuan-Fei Wang, Run-Ping Miao, Xiao Jin, Hui-Hui Wang, Yong-Zheng Chen and Nan-Wei Wan*, ","doi":"10.1021/acscatal.4c02122","DOIUrl":null,"url":null,"abstract":"<p >Spiro-oxazolidinones are highly valuable compounds in the fields of medicinal and organic chemistry; however, the methods for synthesizing these compounds have not been well established. Herein, we present a biocatalytic methodology for the construction of spiro-oxazolidinones through the halohydrin dehalogenase-catalyzed ring expansion of spiro-epoxides. By performing screening and protein engineering of halohydrin dehalogenases, both chiral and racemic spiro-oxazolidinones were synthesized in 24–47% yields (90–98% <i>ee</i>) and 69–98% yields, respectively. The biocatalytic method was also applied to the efficient synthesis of the drug fenspiride at a high substrate concentration of 200 mM (44 g/L). In addition, a chemo-enzymatic strategy was proposed to overcome the limitation of the maximum 50% yield inherent in the kinetic resolution process. Moreover, large-scale synthesis and representative transformations of the spiro-oxazolidinones were carried out to provide additional evidence of the practicality and applicability of the biocatalytic approach.</p>","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":null,"pages":null},"PeriodicalIF":11.3000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biocatalytic Construction of Spiro-Oxazolidinones via Halohydrin Dehalogenase-Catalyzed Ring Expansion of Spiro-Epoxides\",\"authors\":\"Jin-Mei Ma, Yuan-Fei Wang, Run-Ping Miao, Xiao Jin, Hui-Hui Wang, Yong-Zheng Chen and Nan-Wei Wan*, \",\"doi\":\"10.1021/acscatal.4c02122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Spiro-oxazolidinones are highly valuable compounds in the fields of medicinal and organic chemistry; however, the methods for synthesizing these compounds have not been well established. Herein, we present a biocatalytic methodology for the construction of spiro-oxazolidinones through the halohydrin dehalogenase-catalyzed ring expansion of spiro-epoxides. By performing screening and protein engineering of halohydrin dehalogenases, both chiral and racemic spiro-oxazolidinones were synthesized in 24–47% yields (90–98% <i>ee</i>) and 69–98% yields, respectively. The biocatalytic method was also applied to the efficient synthesis of the drug fenspiride at a high substrate concentration of 200 mM (44 g/L). In addition, a chemo-enzymatic strategy was proposed to overcome the limitation of the maximum 50% yield inherent in the kinetic resolution process. Moreover, large-scale synthesis and representative transformations of the spiro-oxazolidinones were carried out to provide additional evidence of the practicality and applicability of the biocatalytic approach.</p>\",\"PeriodicalId\":9,\"journal\":{\"name\":\"ACS Catalysis \",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.3000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Catalysis \",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acscatal.4c02122\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Catalysis ","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acscatal.4c02122","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Biocatalytic Construction of Spiro-Oxazolidinones via Halohydrin Dehalogenase-Catalyzed Ring Expansion of Spiro-Epoxides
Spiro-oxazolidinones are highly valuable compounds in the fields of medicinal and organic chemistry; however, the methods for synthesizing these compounds have not been well established. Herein, we present a biocatalytic methodology for the construction of spiro-oxazolidinones through the halohydrin dehalogenase-catalyzed ring expansion of spiro-epoxides. By performing screening and protein engineering of halohydrin dehalogenases, both chiral and racemic spiro-oxazolidinones were synthesized in 24–47% yields (90–98% ee) and 69–98% yields, respectively. The biocatalytic method was also applied to the efficient synthesis of the drug fenspiride at a high substrate concentration of 200 mM (44 g/L). In addition, a chemo-enzymatic strategy was proposed to overcome the limitation of the maximum 50% yield inherent in the kinetic resolution process. Moreover, large-scale synthesis and representative transformations of the spiro-oxazolidinones were carried out to provide additional evidence of the practicality and applicability of the biocatalytic approach.
期刊介绍:
ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels.
The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.