Preparation of Multivalent Carbohydrate Mimetics Based on Enantiopure 1,2-Oxazines by Sonogashira Coupling and Subsequent Reductive Ring-Opening

A modular approach to aryl C-glycosides and their multivalent analogues is presented. Sonogashira coupling reactions connected the key compounds, enantiopure bicyclic 1,2-oxazine derivatives bearing p-bromophenyl substituents, with alkynes. Subsequent hydrogenolyses or a combination of hydrogenolysis and samarium diiodide mediated reductions converted the coupling products into new unnatural amino carbohydrate mimetics with a D-talose configuration. By Glaser coupling reactions we obtained products with a 1,3-diyne linker and divalent compounds derived therefrom. Through Sonogashira reactions of compound 8 with several iodobenzene derivatives, di-, tri-, and tetravalent compounds were prepared in high yields. The subsequent reductive processes converted the 1,2-oxazine moieties into the corresponding aminopyrans. Severe purification problems were solved in most cases by following the appropriate strategies as an apt sequence of steps or by acetylation of the intermediates.