Syntheses and investigations of 2,6-dideoxysugars contained in diverse bioactive compounds

by Mendlik, Matthew T

Advances in carbohydrate synthesis and analysis have led to a greater understanding of the roles of these molecules in biological processes. This knowledge in turn has led to a greater ability to utilize carbohydrate-based pharmaceuticals in manipulating these processes. We have undertaken both synthetic and biological studies to further knowledge in the area of carbohydrate-based pharmaceuticals. These studies include novel syntheses of L-daunosamine and L-ristosamine, as well as intermediates of these sugars that are suitable for glycosylation with diverse acceptors via the benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride (BSP/Tf2O) glycosylation method. Further, we have developed a simplified system by which the roles of carbohydrates in drugs that bind to DNA can be studied. This system makes use of a facile Sonogashira coupling to link propargyl glycosides to aromatic intercalator moieties. These molecules were then evaluated for DNA binding by viscometry, and were assayed for cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cell lines. Clear differences in activities among library compounds were evident, and some compounds evidenced IC50 values of < 20 µg/mL. This system shows potential for use in many other studies.