Strategies for achieving asymmetric catalysis with azaarenes have traditionally fallen short of accomplishing remote stereocontrol, which would greatly enhance accessibility to distinct azaarenes with remote chiral centres. The primary obstacle to achieving superior enantioselectivity for remote stereocontrol has been the inherent rigidity of the azaarene ring structure. Here we introduce an ene-reductase system capable of modulating the enantioselectivity of remote carbon-centred radicals on azaarenes through a mechanism of chiral hydrogen atom transfer. This photoenzymatic process effectively directs prochiral radical centres located more than six chemical bonds, or over 6 Å, from the nitrogen atom in azaarenes, thereby enabling the production of a broad array of azaarenes possessing a remote γ-stereocentre. Finally, results from our integrated computational and experimental investigations underscore that the hydrogen bonding and steric effects of key amino acid residues are important for achieving such high stereoselectivities.
@article{osti_2309735,
author = {Li, Maolin and Harrison, Wesley and Zhang, Zhengyi and Yuan, Yujie and Zhao, Huimin},
title = {Remote stereocontrol with azaarenes via enzymatic hydrogen atom transfer},
annote = {Strategies for achieving asymmetric catalysis with azaarenes have traditionally fallen short of accomplishing remote stereocontrol, which would greatly enhance accessibility to distinct azaarenes with remote chiral centres. The primary obstacle to achieving superior enantioselectivity for remote stereocontrol has been the inherent rigidity of the azaarene ring structure. Here we introduce an ene-reductase system capable of modulating the enantioselectivity of remote carbon-centred radicals on azaarenes through a mechanism of chiral hydrogen atom transfer. This photoenzymatic process effectively directs prochiral radical centres located more than six chemical bonds, or over 6 Å, from the nitrogen atom in azaarenes, thereby enabling the production of a broad array of azaarenes possessing a remote γ-stereocentre. Finally, results from our integrated computational and experimental investigations underscore that the hydrogen bonding and steric effects of key amino acid residues are important for achieving such high stereoselectivities.},
doi = {10.1038/s41557-023-01368-x},
url = {https://www.osti.gov/biblio/2309735},
journal = {Nature Chemistry},
issn = {ISSN 1755-4330},
number = {2},
volume = {16},
place = {United States},
publisher = {Nature Publishing Group},
year = {2023},
month = {11}}
Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States); Univ. of Illinois at Urbana-Champaign, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)