Synthesis of N-(β-D-glucopyranosyl)- and N-(2-acetamido-2-deoxy-β-D-glucopyranosyl) amides as inhibitors of glycogen phosphorylase

Abstract

2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl- and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl azides were transformed into the corresponding per-O-acetylated N-(β-D-glycopyranosyl) amides via a PMe3 mediated Staudinger protocol (generation of N-(β-D-glycopyranosyl)imino-trimethylphosphoranes followed by acylation with carboxylic acids, acid chlorides or anhydrides). The deprotected compounds obtained by Zemplén deacetylation were evaluated as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitor of this series has been N-(β-D-glucopyranosyl) 3-(2-naphthyl)-propenoic amide (Ki=3.5μM).