Synthesis of ring-expanded homologs of 3-amino pyranosides

Abstract

Amino pyranosides are an important component of natural products like vancomycin and erythromycin. The amine moiety mediates interactions with the biological targets of the compounds and it also influences physicochemical properties. Seven-membered ring septanose carbohydrates hold potential as ring-expanded glycomimetics of pyranosides. Methods for the synthesis of septanose carbohydrates are an essential pre-requisite for their broader application in chemical glycobiology and medicinal chemistry. Here we present the first reported synthesis of 3-aminoseptanosides. Starting from d-ribofuranose, the synthesis Key steps in the sequence include addition by allyl Grignard to a furanosyl amine, ozonolysis, and glycosidation to form the seven-membered ring. Importantly, glycosidation with alcohols like propargyl alcohol introduced a reactivity handle onto the aglycon. Propargyl 3-amino septanosides were subjected to alkyne-azide click cycloaddition reactions with representative azides. This exercise illustrated the post-glycosylation diversification of septanosides, linking our interest in ring-expanded glycomimetics and methods for preparing collections of glycosylated small molecules.