Diversity oriented combinatorial synthesis of multivalent glycomimetics through a multicomponent domino process.

Abstract

Both multicomponent reactions and diversity oriented synthesis are indispensable tools for the modern medicinal chemist. However, their employment for the synthesis of multivalent glycomimetics has not been exploited so far although the importance that such compounds play in exploring multivalency on glycoside inhibition. Herein, we report the combinatorial synthesis of diversity oriented hetero di- and trivalent glycomimetics through a multicomponent domino process. The process is high yielding and very general, working efficiently with easily accessible sugar starting materials such as glycosylamines, glycosylazides, and glycosylisothiocyanates, having the reactive functional groups tethered either directly to the anomeric carbon, through a suitable linker, or to the primary 6 position of hexoses (or 5 position of pentoses), leading, in the latter case, to glycomimetics with artificial enzymatically stable backbone. The process has been also exploited for the multicomponent synthesis of aminoglycoside (neomycin) conjugates.