Abstract
Heparan sulfate (HS) regulates numerous biological processes, but it occurs naturally as a heterogeneous mixture of sulfated complex glycans. Therefore, pursuing a broadly effective approach for homogeneous HS synthesis to advance biological studies has been an outstanding challenge in glycoscience. By merging the catalytic power of sulfotransferases (SULTs) with two distinct iron-catalyzed glycosylation reactions, we report herein a highly stereoselective and generally applicable HS assembly strategy. Every glycosidic linkage in HS was assembled by one of these iron-catalyzed, entirely stereoselective glycosylation reactions. An array of sulfate groups that are essential to HS’s function were installed at their desired locations via the SULT-controlled sulfation of HS precursors. This general approach is showcased in the synthesis of an anticoagulant HS hexasaccharide and other full-length precursors of HS octasaccharides.