Non-native Intramolecular Radical Cyclization Catalyzed by a B12 -Dependent Enzyme.
Angew Chem Int Ed Engl
; 62(51): e202312893, 2023 Dec 18.
Article
en En
| MEDLINE
| ID: mdl-37874184
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.
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1
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MEDLINE
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Factores de Transcripción
/
Vitamina B 12
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos