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 degrees C in the presence of typical carbohydrate acceptors, this donor gives high yields of the corresponding sialosides with exquisite -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 -sialosides with tris(trimethylsilyl)silane or allyltris(trimethylsilyl)silane results in replacement of the C5N5 bond by a CH or a CC 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 -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.