Syntheses of Peptidomimetics Based on Pyranose and Polyhydroxylated Piperidine Scaffolds

Paul   V.   Murphy; Julie   L.   Dunne

doi:10.2174/157017906778699530

Abstract

There has been significant progress in application of pyranoses and related compounds towards drug discovery and development. This review focuses on strategies for grafting of pharmacophore groups at selected positions on pyranoside and related iminosugar scaffolds. Recent developments in the solid phase synthesis of prospecting combinatorial libraries, syntheses of pyranose based sugar amino acids (SAAs) and other scaffolding for peptidomimetics are included. Although no drug molecule has been developed a number of novel potent ligands for receptors have been identified. It has been shown that these pyranoside derivatives could have improved cellular permeability over peptides. Progress in this area is continually dependant on advances in synthetic carbohydrate chemistry both in solution and on solid phase. These include the development of orthogonal protecting group strategies, strategies for regioselective manipulation of pyranoside hydroxyl groups and strategies that could take increasing advantage of chemoselective reactions. In addition a greater understanding of structural carbohydrate chemistry and the preferred orientations of groups attached to pyranose scaffolds may facilitate synthesis of more potent ligands for receptors.

Keywords: nojirimycin, Somatostatin antagonist, D-allopyranose, carbohydrate-based peptidomimetics, Lipidic peptidomimetics, fibrinogen receptor antagonist