Enantioselective decarboxylative alkylation using synergistic photoenzymatic catalysis

Shang Zheng Sun, Bryce T. Nicholls, David Bain, Tianzhang Qiao, Claire G. Page, Andrew J. Musser, Todd K. Hyster

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Photoenzymatic catalysts are attractive for stereoselective radical reactions because the transformation occurs within tunable enzyme active sites. When using flavoproteins for non-natural photoenzymatic reactions, reductive mechanisms are often used for radical initiation. Oxidative mechanisms for radical formation would enable abundant functional groups, such as amines and carboxylic acids, to serve as radical precursors. However, excited state flavin is short-lived in many proteins because of rapid quenching by the protein scaffold. Here we report that adding an exogenous Ru(bpy)32+ cofactor to flavin-dependent ‘ene’-reductases enables the redox-neutral decarboxylative coupling of amino acids with vinylpyridines with high yield and enantioselectivity. Additionally, stereo-complementary enzymes are found to provide access to both enantiomers of the product. Mechanistic studies indicate that Ru(bpy)32+ binds to the protein, helping to localize radical formation to the enzyme’s active site. This work expands the types of transformation that can be rendered asymmetric using photoenzymatic catalysis and provides an intriguing mechanism of radical initiation. [Figure not available: see fulltext.].

Original languageEnglish (US)
JournalNature Catalysis
DOIs
StateAccepted/In press - 2023

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Bioengineering
  • Biochemistry
  • Process Chemistry and Technology

Fingerprint

Dive into the research topics of 'Enantioselective decarboxylative alkylation using synergistic photoenzymatic catalysis'. Together they form a unique fingerprint.

Cite this