A biocatalytic platform for the stereoselective synthesis of diverse atropisomeric compounds using engineered
Xiaochen Cai1, Dong Cui1, Yuchen Chu1
1State Key Laboratory of Green Chemical Synthesis and Conversion, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.
Abstract:
Atropisomeric compounds are widely distributed in natural products and pharmaceuticals and serve as key scaffolds in asymmetric catalysis. Despite their remarkable structural diversity, current synthetic efforts have primarily focused on C-C biaryl atropisomers, while the synthesis of other classes of atropisomeric compounds has been much less explored. Biocatalysis offers precise control over the stereoselectivity of reactions, however, its application in the synthesis of atropisomeric compounds remains at an early stage. In this work, we report a versatile biocatalytic platform that integrates metalloenzyme-catalyzed reduction reactions to access a broad array of structurally diverse atropisomeric compounds, including C-N atropisomers, diaryl ethers, and styrene derivatives, with high yields and excellent enantioselectivities. Molecular dynamics simulations provided mechanistic insights into the origin of the high stereoselectivity, and this study expands the repertoire of metalloenzyme-catalyzed, new-to-nature transformations for the synthesis of valuable molecules.
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