Synthesis and Glycosidase Inhibitory Activity of Five Stereoisomers of 5-Amino-5-C-methyl-1,2,3,4-cyclopentanetetrol

Abstract

In order to elucidate the essential core structure of potent α-mannosidase inhibitors, e.g. mannostatin A, 5-amino-5-C-methyl-1,2,3,4-cyclopentanetetrols 4-8 were designed and synthesized by a base-catalyzed nitro aldol condensation of nitroethane and the dialdehyde derived by periodate oxidation of DL-1,2-O-cyclohexylidene-myo-inositol, followed by reduction and deprotection. Biological assay of the five stereoisomers thus obtained for the six glycosidases has demonstrated the DL-(1,2/3,4,5) and (1,2,3,4,5/0) isomers to be moderate α-mannosidase inhibitors, suggesting that the all-cis configuration of the amino and three hydroxy groups on the cyclopentane ring plays a role in exhibiting inhibitory activity.