New catalytic strategies for DNA and RNA alkylation using rhodium (II) and copper (I) carbenes - a versatile tool for applications in chemical biology

摘要

A variety of nucleic acid substrates were catalytically alkylated with rhodium(II) and copper(I)-carbenoids generated from diazocarbonyl compounds. The alkylation took place via an N-H insertion reaction selectively targeting the nucleobases in single-stranded DNA and RNA motifs. The use of alkyne-functionalized diazo carbonyl compounds allowed combination of the alkylation approach with the copper(I)-catalyzed alkyne-azide cycloaddition (copper ‘click’ chemistry) in a straightforward modification protocol, unlocking the potential for a whole new array of biologically relevant product structures. In the case of copper(I) the concurrent introduction of an alkyne function in the nucleic acid via amine alkylation and its coupling to the appropriate azide in a auto-tandem catalytic process utilizing a single catalyst offers a unique ‘one-pot’ strategy for biomolecular diversification.