Synthesis of <i>C</i>-acyl furanosides <i>via</i> the cross-coupling of glycosyl esters with carboxylic acids

Abstract

<i>C</i>-Acyl furanosides are versatile synthetic precursors to a variety of natural products, nucleoside analogues, and pharmaceutical molecules. This report addresses the unmet challenge in preparing <i>C</i>-acyl furanosides by developing a cross-coupling reaction between glycosyl esters and carboxylic acids. A key step is the photoredox activation of the glycosyl ester, which promotes the homolysis of the strong anomeric C-O bond through CO₂ evolution to afford glycosyl radicals. This method embraces a large scope of furanoses, pyranoses, and carboxylic acids, and is readily applicable to the synthesis of a thymidine analogue and diplobifuranylone B, as well as the late-stage modification of (+)-sclareolide. The convenient preparation of the redox active glycosyl ester from native sugars and the compatibility with common furanoses exemplifies the potential of this method in medicinal chemistry.