Synthesis and biological evaluation of bicyclic iminosugar derivatives as inhibitors of glycosidases

During this work, five pyrrolizidine derivatives and one isoxazolidine derivative have been synthetized in order to evaluate their biological activities towards glycosidases, related to their configurations and type of bridge functionalities between the bicyclic iminosugar moiety and the aromatic part of the molecules. The final pyrrolizidine derivatives have been synthetized through click reactions (urea forming reaction, thiourea forming reaction and CuAAC reaction) performed on a common amino-pyrrolizidine precursor. The final isoxazolidine derivative has been synthetized through a CuAAC reaction. In addition, an indolizidine scaffold was obtained through a ring-closing metathesis on a dialkenyl pyrrolidine. This bicyclic compound could be of interest as intermediate for the synthesis of indolizidine derivatives with potential as glycosidase inhibitors. Biological evaluation towards glycosidases of the final six compounds synthetized in this work revealed that all of these compounds show inhibition towards almonds’ β-glucosidase and/or jack beans’ α-mannosidase.