Synthesis of 2,3,4,6-Tetra-O-acetyl-α-d-mannopyranosyl Azide

Among natural glycosylated structures, glycoproteins and glycopeptides are of signicant biological interest due to their widespread roles in cell recognition and cell adhesion, and improving absorption of poorly bioavailable drugs and peptides by enhancing membrane transport.1 The azido function usually serves as a latent amino group and therefore azido glycosides represent key intermediates in the synthesis of corresponding glycosyl amino acids.2 Another useful application of azido glycosides has recently been highlighted by the use of the CuI-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition reaction to efciently afford various N-glycosyl-triazole

Experimental ..........................................................................................................264 General Methods ...............................................................................................264 2,3,4,6-Tetra-O-acetyl-α-d-mannopyranosyl azide (2) .....................................264

Acknowledgments ..................................................................................................265 References ..............................................................................................................266

mimetics.3 In this context, various synthetic methods have been developed to introduce the azide function at the anomeric position, using corresponding glycosyl halides,4 phosphates,5 or 1,2 cyclic sultes.6 Unlike strategies that involve low stability precursors, modest yields, or formation of anomeric mixture, 2,3,4,6-tetraO-acetyl-α-d-mannopyranosyl azide was obtained7 in (80% to nearly theoretical) yields from the corresponding pentaacetate and azidotrimethylsilane (TMSN3) by a Lewis acid-catalyzed reaction. Here we describe the high yielding synthesis of 2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl azide from 1-O-acetyl derivative 1 and TMSN3 through a SnCl4-catalyzed reaction in CH2Cl2.