Title: Design and Synthesis of Aminocyclopentanol Glycosidase Inhibitors: Modification of Mannostatin A and Trehazolamine
VOLUME: 6 ISSUE: 1
Author(s):Seiichiro Ogawa, Miki Kanto and Chikara Uchida
Affiliation:Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama, 223-8522 Japan.
Keywords:Drug design, glycosidase inhibitors, aminocyclitols, bioactive cyclitols, natural product syntheses, diastereoselective synthesis, chemical modification, structure-inhibitory activity relationships
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.
