NIH Reporter #5R35GM150902-04

Carbon isotope exchange mediated by vanadium complexes

Award for research on vanadium-based catalysts to enable carbon isotope exchange for labeling pharmaceuticals and natural products, supporting drug development and imaging studies.

Description

The proposed studies focus on the design, synthesis, and development of vanadium-based catalysts to perform carbon isotope exchange via =*CH2 (*C = 11C, 13C, and 14C) group transfer between terminal olefins. This emerging area allows for the direct incorporation of carbon-14 isotope into target compounds for metabolic and pharmacokinetic studies, as well as the integration of carbon-11 into pharmaceuticals for positron emission tomography. The innovation involves developing olefin metathesis catalysts based on vanadium, utilizing a highly polarized V=C bond, enabling regioselective formation of metallacyclobutane and reversible =CH2 transfer without cross-products or ethylene formation. The method uses accessible labeled iodomethane (*CH3I) as a carbon isotope source and can be expanded to alkyl-containing bioactive molecules through tandem dehydrogenation/olefin metathesis strategies. This approach aims to synthesize isotopically labeled pharmaceuticals and natural products efficiently.

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