Biocatalytic Alkylation of Ambident Nucleophiles Enables Selective N-Functionalization of Heterocycles and Late-Stage Modifications.

ABSTRACT: The alkylation with electrophilic haloalkanes is a key methodology in chemical synthesis to build desired molecules. Although alkylation of compounds bearing a single nucleophilic site is routine, the selective alkylation of polyfunctional molecules with multiple competing nucleophilic positions of comparable reactivity is often very challenging. In this work, we report a generalizable solution for selective alkylation chemistry that combines the selectivity of enzyme catalysis with the reactivity of off-the-shelf alkylation reagents. We employ engineered transferases in a modular cyclic cascade and use functionalized N-heteroarenes as challenging proof-of-concept substrates. This catalytic alkylation approach is mild, highly chemo- and regioselective, proceeds on gram-scale, provides rapi

SUBMITTER: Ospina F 

PROVIDER: S-EPMC12402838 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature