Stereoselective Synthesis of the Equatorial Glycosides of Legionaminic Acid.

The synthesis of a legionaminic acid donor from N-acetylneuraminic acid in 15 steps and 17% overall yield is described. Activation of the adamantanyl thioglycoside in the donor with N-iodosuccinimide and trifluoromethanesulfonic acid in dichloromethane and acetonitrile at -78 °C in the presence of primary, secondary and tertiary alcohols affords the corresponding glycosides in excellent yield and good to excellent equatorial selectivity. In particular, coupling to the 4-OH of a suitably protected neuraminic acid derivative affords a disaccharide that closely resembles the glycosidic linkage in the polylegionaminic acid from the lipopolysaccharide of the Legionella pneumophila virulence factor. A straightforward deprotection sequence enables conversion of the protected glycosides to the free N,N-diacetyllegionaminic acid glycosides.