{"title":"用化学-酶法制备光学产率高的伊非那唑。","authors":"Zhiran Ju, Zhiyun Li, Menglan Li, Saili Xu, Kumaravel Kaliaperumal and Fen-Er Chen*, ","doi":"10.1021/acs.joc.3c01641","DOIUrl":null,"url":null,"abstract":"<p >Herein, we present a novel and ecofriendly biocatalytic approach for synthesizing efinaconazole (<b>7</b>), a clinically used antifungal agent. This method involves utilizing benzaldehyde lyase (BAL) to catalyze the crucial benzoin condensation step in the ketone precursor. Treating 2,4-difluorobenzaldehyde with BAL in the presence of thiamin-diphosphate (ThDP) and Mg<sup>2+</sup> resulted in the formation of α-hydroxy ketone which then underwent the preparation of <b>7</b>. This innovative approach not only provides a greener alternative but also offers significant advantages over the traditional chemical process. Through our efforts and development work, we have established efficient and scalable procedures that enable the production of <b>7</b> in a moderate 38% yield.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"88 20","pages":"14803–14808"},"PeriodicalIF":3.3000,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Chemo-Enzymatic Approach for Preparing Efinaconazole with High Optical Yield\",\"authors\":\"Zhiran Ju, Zhiyun Li, Menglan Li, Saili Xu, Kumaravel Kaliaperumal and Fen-Er Chen*, \",\"doi\":\"10.1021/acs.joc.3c01641\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Herein, we present a novel and ecofriendly biocatalytic approach for synthesizing efinaconazole (<b>7</b>), a clinically used antifungal agent. This method involves utilizing benzaldehyde lyase (BAL) to catalyze the crucial benzoin condensation step in the ketone precursor. Treating 2,4-difluorobenzaldehyde with BAL in the presence of thiamin-diphosphate (ThDP) and Mg<sup>2+</sup> resulted in the formation of α-hydroxy ketone which then underwent the preparation of <b>7</b>. This innovative approach not only provides a greener alternative but also offers significant advantages over the traditional chemical process. Through our efforts and development work, we have established efficient and scalable procedures that enable the production of <b>7</b> in a moderate 38% yield.</p>\",\"PeriodicalId\":57,\"journal\":{\"name\":\"Journal of Organic Chemistry\",\"volume\":\"88 20\",\"pages\":\"14803–14808\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-10-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Organic Chemistry\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.joc.3c01641\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Organic Chemistry","FirstCategoryId":"1","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.joc.3c01641","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
A Chemo-Enzymatic Approach for Preparing Efinaconazole with High Optical Yield
Herein, we present a novel and ecofriendly biocatalytic approach for synthesizing efinaconazole (7), a clinically used antifungal agent. This method involves utilizing benzaldehyde lyase (BAL) to catalyze the crucial benzoin condensation step in the ketone precursor. Treating 2,4-difluorobenzaldehyde with BAL in the presence of thiamin-diphosphate (ThDP) and Mg2+ resulted in the formation of α-hydroxy ketone which then underwent the preparation of 7. This innovative approach not only provides a greener alternative but also offers significant advantages over the traditional chemical process. Through our efforts and development work, we have established efficient and scalable procedures that enable the production of 7 in a moderate 38% yield.
期刊介绍:
Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.