Structure-Selective Catalytic Alkylation of DNA and RNA

摘要

Deciphering the complex puzzle of nucleic acid (NA) chemistry and biology has proven incredibly difficult and continues unabated after more than a century.Chemists have begun to recognize that the extraordinary informational and structural properties that have made NAs so fundamental in biology could be exploited in other contexts. Simple, selective chemical strategies to modify NAs would therefore have a significant impact on studying their varied functions as well as repurposing their special abilities, yet most extant tools to target them are unselective or labor intensive. Although a number of reports exploring the potential of organometallic catalysis in biological environments have recently appeared, such strategies have not yet been applied towards selective NA alkylation. But untapped potential is suggested by the ability to tune the reactivity of metal complexes through judicious ligand selection and a number of studies demonstrating the feasibility of metal catalysis with DNA as a ligand. We establish herein that rhodium-catalyzed carbene transfer is a viable means of achieving the selective alkylation of a variety of NAs.