Modular Synthesis of Nucleoside Diphosphate Sugar Analogues Using Chlorosulfonyl Isocyanate and Dichlorophosphoryl Isocyanate

Abstract

Pyrophosphates are central to biology, and synthetic pyrophosphate isosteres are widely sought to create biomimetic molecules to study diverse biochemical processes. We describe a flexible, modular synthesis of nucleoside diphosphate sugar analogues by linking carbasugars and nucleosides with the dual electrophilic reagents chlorosulfonyl isocyanate and dichlorophosphoryl isocyanate, introducing sulfonyl- and phosphoryl-carbamate linkages as pyrophosphate isosteres, respectively. The resulting GDP-fucose and UDP-GlcNAc analogues may inhibit glycosyltransferases and serve as tools for studying pyrophosphate-processing enzymes.