Backbone-Anchoring, Solid-Phase Synthesis Strategy To Access a Library of Peptidouridine-Containing Small Molecules

Abstract

Nucleoside diphosphate sugar (NDP-sugar) substrates provide the inspiration for nucleoside analogue inhibitor scaffolds. By employing solid-phase synthesis, we provide a method to access a library of peptidouridine inhibitors with both minimal compound handling and purification steps. Specifically, this strategy is exemplified by generating uridine diphosphate sugar (UDP-sugar) mimics, which allow for compound elaboration by altering the dipeptide composition, the N-terminal linkage, and a pendant aryl group. To exemplify the versatility, 41 unique nucleoside analogues are presented.