Expanding Biocatalysis for Organosilane Functionalization: Enantioselective Nitrene Transfer to Benzylic Si–C–H Bonds
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1.
California Institute of Technology
Abstract
Directed evolution has the potential to enable abiological chemistry by engineering natural enzymes to function on non-natural substrates. In this study, we expanded the repertoire of enzymatic functionalization of organosilicon compounds by evolving a cytochrome P450 variant for the selective amidation of organosilanes, resulting in the production of functionalized α-aminosilanes with remarkable enantioselectivities (up to 333 TTN and >99% ee). The evolved enzyme catalyzes this nitrene transfer reaction on benzylic Si–C–H bonds under aerobic conditions with up to 125-fold higher yield compared to its progenitor, evolved previously for amidation of unactivated C–H bonds in carbon-based molecules.
Copyright and License
© 2023 American Chemical Society. This publication is licensed under these Terms of Use.
Acknowledgement
This work was supported by the Dow University Partnership Initiative (227027AO and 227027AU) to F.H.A. The authors thank Dr. Kathleen M. Sicinski for assistance with the recombination experiment and Dr. Asik Hossain for assistance with chiral SFC data collection. The authors also thank Dr. Michael Takase for assistance with X-ray crystallographic data collection, Dr. Mona Shahgoli for assistance with HRMS data collection, and Dr. Sabine Brinkmann-Chen for helpful discussions and comments on the manuscript.
Contributions
A.D. and Y.L. contributed equally.
Conflict of Interest
The authors declare no competing financial interest.
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Additional details
- ISSN
- 2155-5435
- Dow Chemical (United States)
- 227027AO
- Dow Chemical (United States)
- 227027AU