National Institute of General Medical Sciences 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 bioactive molecules, 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. Carbon isotope exchange allows incorporating carbon-14 isotope directly 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 and ethylene formation. The method uses accessible labeled iodomethane (*CH3I) as a carbon isotope source and will be expanded to alkyl-containing bioactive molecules using tandem dehydrogenation/olefin metathesis strategies. This approach aims to facilitate the synthesis of isotopically labeled pharmaceuticals and natural products.

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