Title
Chemoselective Cyclopropanation over Carbene Y-H insertion Catalyzed by an Engineered Carbene Transferase
Author
Eric J. Moore, Viktoria Steck, Priyanka Bajaj, Rudi Fasan
Year
2018
Journal
The Journal of Organic Chemistry
Abstract
Hemoproteins have recently emerged as promising biocatalysts for promoting a variety of carbene transfer reactions including cyclopropanation and Y—H insertion (Y = N, S, Si, B). For these and synthetic carbene transfer catalysts alike, achieving high chemoselectivity toward cyclopropanation in olefin substrates bearing unprotected Y—H groups has proven remarkably challenging due to competition from the more facile carbene Y—H insertion reaction. In this report, we describe the development of a novel artificial metalloenzyme based on an engineered myoglobin incorporating a serine-ligated Co-porphyrin cofactor that is capable of offering high selectivity toward olefin cyclopropanation over N—H and Si—H insertion. Intramolecular competition experiments revealed a distinct and dramatically altered chemoselectivity of the Mb(H64V,V68A,H93S)[Co(ppIX)] variant in carbene transfer reactions compared to myoglobin based variants containing the native histidine-ligated heme cofactor or other metal/proximal ligand substitutions. These studies highlight the functional plasticity of myoglobin as a ‘carbene transferase’ and illustrate how modulation of the cofactor environment within this metalloprotein scaffold represents a valuable strategy for accessing carbene transfer reactivity not exhibited by naturally occurring hemoproteins or transition metal catalysts.
Full Article
Instrument
J-1100
Keywords
Circular dichroism, Secondary structure, Thermodynamics, Thermal stability, Organic chemistry, Biochemistry