Chemoenzymatic synthesis of heparan sulfate tetrasaccharide from a N-acetyl-α-d-glucosamine-O-methylglycoside acceptor

Abstract Heparan sulfate tetrasaccharide 2 was efficiently prepared in seven steps through chemoenzymatic synthesis. A monosaccharide 5 , N -acetyl-α- d -glucosamine- O -methylglycoside (GlcNAc-OMe), was successfully used as an acceptor in a heparosan synthase (pmHS2)-catalyzed glycosylation reaction. This avoided the multi-step synthesis of a more complex disaccharide acceptor 3 , greatly simplifying the route to tetrasaccharide target 2 . This approach provides a critical tetrasaccharide intermediate for subsequent chemoenzymatic transformation to fondaparinux and its analogues.