Synthesis of N-(β-d-glucopyranosyl) monoamides of dicarboxylic acids as potential inhibitors of glycogen phosphorylase

O-Peracetylated N-(β-d-glucopyranosyl)imino trimethylphosphorane obtained in situ from 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl azide and PMe3 was reacted with saturated and unsaturated aliphatic and aromatic dicarboxylic acids, or their anhydrides, or monoesters to give the corresponding N-(β-d-glucopyranosyl) monoamides of dicarboxylic acids or derivatives. The acetyl protecting groups were removed according to the Zemplén protocol to give a series of compounds which showed moderate inhibitory effects against rabbit muscle glycogen phosphorylase b. The best inhibitor was 3-(N-β-d-glucopyranosyl-carbamoyl)propanoic acid (7) with Ki = 20 μM.

Graphical abstractThe best inhibitor of the series (linker = –CH2CH2–, R = H) showed Ki = 20 μM against rabbit muscle glycogen phosphorylase b.Figure optionsDownload full-size imageDownload as PowerPoint slide