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

Abstract

O-Peracetylated N-(β- d-glucopyranosyl)imino trimethylphosphorane obtained in situ from 2,3,4,6-tetra- O-acetyl-β- d-glucopyranosyl azide and PMe 3 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 K i = 20 μM.