Effective Synthesis of α-d-GlcN-(1→4)-d-GlcA/l-IdoA Glycosidic Linkage under Gold(I) Catalysis

Abstract

An effective glycosylation procedure for the stereoselective construction of the α-d-GlcN-(1→4)-d-GlcA/l-IdoA glycosidic linkage found in heparin and heparan sulfate is reported. The condensation occurs between 2-deoxy-2-azido-d-glucopyranosyl (d-GlcN) ortho-hexynylbenzoate donors and uronate acceptors (d-GlcA/l-IdoA) under mild gold(I)-catalyzed conditions. Optimal results are obtained when performing the reaction in CH2Cl2, from -72°C to room temperature in the presence of 4Å molecular sieves and under the promotion of [Ph3PAuCl]/AgOTf or [(1,1-bis-(diphenylphosphino)methane)(AuCl)2]/AgOTf as a source of the gold(I) catalyst. A donor/acceptor ratio of 3:1 as well as a loading of 0.6equivalents of the gold(I) catalyst are essential to attain high yields and αselectivity, particularly for the [1+1] and [1+2] glycosylations.