Synthesis and Biological Evaluation of Aza-<i>C</i>-disaccharides: (1→6), (1→4), and (1→1) Linked Sugar Mimics

Abstract

The synthesis of (1→6), (1→4), and (1→1) linked aza-C-disaccharides, a novel class of glycomimetic compounds, is described. The polyhydroxylated piperidine ring was synthesized using vinyl bromide 11 as a common intermediate which was synthesized de novo from bromobenzene utilizing the microbial oxidation metabolite bromodiol 10. A Suzuki coupling of 11 with an alkylboron reagent derived from olefinated carbohydrate precursors via hydroboration was used to form the C-glycosidic bond. Ozonolysis and selective reduction of the resultant carbonyl functions served to produce the azasugar ring. Fully deprotected aza-C-disaccharides were obtained upon acidic deprotection. Biological screening of the title compounds against several common glycosidase enzymes as well as in vitro anti-HIV assays are reported.