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FULL PAPER DOI: 10.1002/ejoc.200700333 Synthetic Routes to Three Novel Scaffolds for Potential Glycosidase Inhibitors Michael Rommel,[a] Alexander Ernst,[b][‡] and Ulrich Koert*[a] Keywords: Synthesis / Ketalisation / Hydroxypyridine / Cyclopentane / Glycosidase inhibitor Efficient syntheses of three novel scaffolds for potential β- was accessible through a sequence of substituent directed glycosidase inhibitors were developed: The first consists of a ortho-lithiations. Selected compounds were tested as inhibi- 2,7-dioxabicyclo[2.2.1]heptane derivative, which was pre- tors for a number of glycosidases. Three nicotinic acid deriva- pared by an intramolecular ketalisation. The second scaffold tives were found to be selective β-glucosidase inhibitors. consists of a hydroxylated cyclopentylamine, which could be synthesised stereoselectively from 2-azabicyclo[2.2.1]hept-5- (© Wiley-VCH Verlag GmbH Co. KGaA, 69451 Weinheim, en-3-one. The third scaffold, a 4,5-dihydroxynicotinic acid, Germany, 2007) Introduction The oligosaccharides of the glycocalix are involved in many disease-relevant cellular molecular-recognition events. Glycosidases, which interfere and control the cellular oligo- saccharide processing are therefore an important class of targets for pharmaceutical research. For that reason, gly- cosidase inhibitors present an important substance class for drug development.[1] Currently, glycosidase inhibitors are established for the treatment of diabetes[2] and influenza.[3] Furthermore, their function as antiviral agents is also useful for the development of potential applications against hepa- titis,[4] HIV[5] and cancer.[6] Representative examples for β- Figure 1. Naturally occurring and synthetic β-glycosidase inhibi-