Overcoming reactivity limitations in glycosylation with a novel protecting group.

Abstract

Controlling stereoselectivity of glycosylation reactions is an immense task in practically all glycosylations that are not assisted by the neighboring participating groups. Hydrogen-bond-mediated aglycone delivery (HAD) reaction is known to provide an efficient stereocontrolling handle in reactions with glycosyl donors bearing a picoloyl (Pico) protecting group. To further improve this methodology, herein we report a rationally designed 6-(methoxycarbonyl)picoloyl (Dent) protecting group. The Dent group provided somewhat unexpected results. On the one hand, in most applications, the stereoselectivity was lower than that achieved with the respective glycosyl donors equipped with the Pico group. On the other hand, quite remarkably, Dent-protected glycosyl donors were found to be extremely reactive, which led to very efficient and swift reactions in cases where Pico-protected glycosyl donors lacked efficiency or failed to produce preparatively useful results.