Synthetic Routes to Three Novel Scaffolds for Potential Glycosidase Inhibitors
Efficient syntheses of three novel scaffolds for potential β-glycosidase inhibitors were developed: The first consists of a 2,7-dioxabicyclo[2.2.1]heptane derivative, which was prepared by an intramolecular ketalisation. The second scaffold consists of a hydroxylated cyclopentylamine, which could be synthesised stereoselectively from 2-azabicyclo[2.2.1]hept-5-en-3-one. The third scaffold, a 4,5-dihydroxynicotinic acid, was accessible through a sequence of substituent directed ortho-lithiations. Selected compounds were tested as inhibitors for a number of glycosidases. Three nicotinic acid derivatives were found to be selective β-glucosidase inhibitors.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)