Biocatalytic Synthesis of Metaxalone and Its Analogues

作者：Zhu‐Xiang Wang, Hong‐Kang Fu, Xin-Yu Da, Huihui Wang, Bao‐Dong Cui, Wen‐Yong Han, Yong‐Zheng Chen, Nan‐Wei Wan · 发表于：Organic Letters · 年份：2023 · DOI：10.1021/acs.orglett.3c01752 · 被引用次数：14 · 研究领域：Enzyme Catalysis and Immobilization、Chemical Synthesis and Reactions、Chemical Synthesis and Analysis

A biocatalytic approach for the synthesis of metaxalone and its analogues was developed based on the reaction of epoxides and cyanate catalyzed by halohydrin dehalogenase. Gram-scale synthesis of chiral and racemic metaxalone was achieved with 44% (98% ee ) and 81% yields, respectively, by protein engineering of the halohydrin dehalogenase HHDHamb from Acidimicrobiia bacterium . Additionally, various metaxalone analogues were synthesized at 28–40% yields (90–99% ee ) for chiral forms and 77–92% yields for racemic forms.