Synthetic analogs of natural glycosides in drug discovery and development

Secondary metabolites, which have vital environmental and allelopathic functions for a host, and long tradition of ethnopharmacological applications preceding modern medicinal use, often occur in their native state as glycosides. The role of sugar moiety looks completely different from plant physiology point of view and from drug discovery and development perspective. Based on a short survey of cases, in which structural modification of natural glycone (saccharide part of a low molecular weight secondary metabolite) resulted in advantageous pharmacological changes, we postulate that glycosides of natural origin can be quite promising as drug leads, based on general rules of drug design. In particular, polyfunctional sugar moieties offer ample opportunities for almost continuous changes in shape, electron density and polarity. By the same token, glycosylation of other biologically active natural products, which are not natively glycosylated, can be viewed as a tool for tune up of their activity in direction of higher efficacy and better selectivity. Despite of considerable advances towards turning enzymatic glycosylations into biotechnological processes, chemical transformations still remain more practical, particularly for synthesis of modified glycosides, both: in research laboratory and in industry.