Abstract

Convenient synthesis of the α-mannosidase inhibitor mannostatin A from myo-inositol is described by a method, which is generally applicable for provision of aminocyclopentanols of biological interest. Elucidation of structure-inhibitory activity relationships was carried out by chemical modification, leading to discovery of a very potent amino(methoxy)cyclopentanetriol. Similar studies of the trehalase inhibitor trehazolin stimulated development of a new type of aminocyclopentanol glycosidase inhibitor featuring ring contract mimicking of valiolamine, with implications for understanding of the structure and activity relationships of glycosidase inhibitors of this type.

Keywords: Drug design, glycosidase inhibitors, aminocyclitols, bioactive cyclitols, natural product syntheses, diastereoselective synthesis, chemical modification, structure-inhibitory activity relationships