Non‐native Intramolecular Radical Cyclization Catalyzed by a B12‐Dependent Enzyme**
Abstract
Despite the unique reactivity of vitamin B12 and its derivatives, B12‐dependent enzymes remain underutilized in biocatalysis. In this study, we repurposed the B12‐dependent transcription factor CarH to enable non‐native radical cyclization reactions. An engineered variant of this enzyme, CarH*, catalyzes the formation γ‐ and δ‐lactams through either redox‐neutral or reductive ring closure with marked enhancement of reactivity and selectivity relative to the free B12 cofactor. CarH* also catalyzes an unusual spirocyclization by dearomatization of pendant arenes to produce bicyclic 1,3‐diene products instead of 1,4‐dienes provided by existing methods. These results and associated mechanistic studies highlight the importance of protein scaffolds for controlling the reactivity of B12 and expanding the synthetic utility of B12‐dependent enzymes.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 14, 2023
- Source ID
- 10.1002/ange.202312893
Entities
People
- Amardeep Kumar
- Jared C Lewis
- Jianbin Li
Organizations
- Army Research Office
- Indiana University
- National Institute of General Medical Sciences
- National Science Foundation