C--linked Glycoside Natural Products: Even better than the real thing
University of Idaho Seed Grant
Sugar-connected compounds (termed glycosides) are found in a variety of organisms with many classified as biologically active. The sugar subunits are often deemed unnecessary and removed from the “active” ingredient. Sugar removal alters the polarity, chemical solubility and biological adsorption characteristics of these molecules and without proper bioavailability can take many fruitful drug candidates out of the screening process. Glycoside linkages and patterning have proven important in molecular recognition pathways (key for determining blood type). We hypothesize that glycoside recognition combined with an active drug ingredient could lead to a more controlled drug-delivery. This proposal describes our aim to synthesize a series of new glycosides, modeled from nature, yet with non-cleavable carbon-carbon bond linkages (C- linkage) allowing for the sugar to stay attached. Salicin, a common anti-inflammatory natural product and salidroside, a common anti-depressive natural product, will be our first targets as potential pharmaceuticals. Synthetically, we will employ known methods taken from our current C-linked pesticide projects to build the various structures. Expanding our C-linked glycoside research niche into pharmaceutical mimics of natural products will lead to the design of a new class of drug; one that goes in fast, works, and leaves.