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

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.