Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization DOI Creative Commons
James G. Zhang, Anthony J. Huls, Jared C. Paris

et al.

Published: Aug. 16, 2024

The trifluoromethyl (–CF3) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made development of synthetic methods for trifluoromethylation. In contrast, there are currently no metal-loenzymes known to catalyze formation C(sp3)‒CF3 bonds. this work, we demonstrate that nonheme iron enzyme, hydroxy-mandelate synthase from Amycolatopsis orientalis (AoHMS), is capable generating CF3 radicals hypervalent iodine(III) reagents and directing them enantioselective alkene azidation. A high-throughput screening (HTS) platform based on Staudinger ligation was established, enabling rapid evaluation AoHMS variants abiological transformation. final opti-mized variant accepts range substrates, producing azidation products up 73% yield 96:4 enanti-omeric ratio (e.r.). biocatalytic can be further extended pentafluoroethyl diazidation by altering reagent. addition, anion competition experiments provide insights into radical rebound process This study not only expands catalytic repertoire metalloenzymes transformations but also creates new enzymatic space organofluorine synthesis.

Language: Английский

Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization DOI Creative Commons
James G. Zhang, Anthony J. Huls, Jared C. Paris

et al.

Published: Aug. 19, 2024

The trifluoromethyl (–CF3) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made development of synthetic methods for trifluoromethylation. In contrast, there are currently no metalloenzymes known to catalyze formation C(sp3)‒CF3 bonds. this work, we demonstrate that nonheme iron enzyme, hydroxymandelate synthase from Amycolatopsis orientalis (AoHMS), is capable generating CF3 radicals hypervalent iodine(III) reagents and directing them enantioselective alkene azidation. A high-throughput screening (HTS) platform based on Staudinger ligation was established, enabling rapid evaluation AoHMS variants abiological transformation. final opti-mized variant accepts range substrates, producing azidation products up 73% yield 96:4 enanti-omeric ratio (e.r.). biocatalytic can be further extended pentafluoroethyl diazidation by altering reagent. addition, anion competition experiments provide insights into radical rebound process This study not only expands catalytic repertoire transformations but also creates new enzymatic space organofluorine synthesis.

Language: Английский

Citations

2
Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization DOI
James G. Zhang, Anthony J. Huls,

Philip M. Palacios

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

The trifluoromethyl (-CF

Language: Английский

Citations

2
Hot off the press DOI
Robert A. Hill, Andrew Sutherland

Natural Product Reports, Journal Year: 2024, Volume and Issue: 41(2), P. 157 - 161

Published: Jan. 1, 2024

A personal selection of 32 recent papers is presented covering various aspects current developments in bioorganic chemistry and novel natural products such as dcalycinumine from Daphniphyllum calycinum .

Language: Английский

Citations

1
Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization DOI Creative Commons
James G. Zhang, Anthony J. Huls, Jared C. Paris

et al.

Published: Aug. 16, 2024

The trifluoromethyl (–CF3) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made development of synthetic methods for trifluoromethylation. In contrast, there are currently no metal-loenzymes known to catalyze formation C(sp3)‒CF3 bonds. this work, we demonstrate that nonheme iron enzyme, hydroxy-mandelate synthase from Amycolatopsis orientalis (AoHMS), is capable generating CF3 radicals hypervalent iodine(III) reagents and directing them enantioselective alkene azidation. A high-throughput screening (HTS) platform based on Staudinger ligation was established, enabling rapid evaluation AoHMS variants abiological transformation. final opti-mized variant accepts range substrates, producing azidation products up 73% yield 96:4 enanti-omeric ratio (e.r.). biocatalytic can be further extended pentafluoroethyl diazidation by altering reagent. addition, anion competition experiments provide insights into radical rebound process This study not only expands catalytic repertoire metalloenzymes transformations but also creates new enzymatic space organofluorine synthesis.

Language: Английский

Citations

1