The Isothiocyanato Moiety: An Ideal Protecting Group for the Stereoselective Synthesis of Sialic Acid Glycosides and Subsequent Diversification

The preparation of a crystalline, peracetyl adamantanyl thiosialoside donor protected by an isothiocyanate group is described. On activation at ?78 °C in the presence of typical carbohydrate acceptors, this donor gives high yields of the corresponding sialosides with exquisite α‐selectivity. The high selectivity extends to the 4‐O‐benzyl‐protected 3‐OH acceptors, which are typically less reactive and selective than galactose 3,4‐diols. Treatment of the α‐sialosides with tris(trimethylsilyl)silane or allyltris(trimethylsilyl)silane results in replacement of the C5? N5 bond by a C? H or a C? C bond. The reaction of the isothiocyanate‐protected sialosides with thioacids generates amides, while reaction with an amine gives a thiourea, which can be converted into a guanidine. The very high α‐selectivities observed with the new donor and the rich chemistry of the isothiocyante function considerably extend the scope for optimization at the sialoside 5‐position.