Complex glycans are directly involved in essential life processes, but it is challenging to precisely assemble them in sufficient quantities with high homogeneity. One major hurdle is that the stereoselectivity in glycosylation often varies with substrates, thus it is difficult to develop an exquisitely selective glycosylation method that is also broadly effective. In particular, searching for a general solution for stereoselective assembly of 1,2-cis-glycosidic bonds is an unsolved challenge. The lecture will focus on the discovery of a mechanistically unique and generally applicable approach for exclusively 1,2-cis-selective glycosylation and on the development of a broadly effective stereospecific glycosylation approach with glycal epoxides.

In this lecture, we will also discuss a glycosaminoglycan (GAG) assembly strategy by merging the catalytic power of sulfotransferases (SULTs) with these two distinct iron-catalyzed glycosylation reactions. Every glycosidic linkage in heparan sulfate (HS) was assembled by one of these iron-catalyzed, entirely stereoselective glycosylation reactions. An array of sulfate groups that are essential to the functions of HS were installed at their desired locations via the SULT-controlled sulfation reactions. Finally, we will present the highly stereoselective and azide-free synthesis of Fondaparinux, the only FDA-approved, non-animal sourced GAG-type anticoagulant medicine.