Sialic acids are acidic monosaccharides with 9-carbon backbone that are found at the outermost of the mammalian cell membrane. They are a family of about 50 naturally derivatives of neuraminic acid, with N-acetyl neuraminic acid being the most common member. Its biological importance, as a terminal component of glycoconjugates, ranges from cell-cell interactions to pathogens attacks. Thus, the stereoselective synthesis of sialic acid-containing glycoconjugates with high yields is very important but unfortunately also a synthetic challenge in the carbohydrate synthesis field.

Regardless tremendous advancement in the field, sialic acid glycosylations (sialylations) are still a limiting factor in the synthesis of complex carbohydrates, which are biologically relevant for the design of therapeutics.

Based on the recent finding by De Meo et. al. on the existence of a conformational equilibrium at the oxacarbenium ion level that suggested positions C-4 and C-7 might be relevant in sialylation reactions; and on the recent reports by Demchenko et. al. on Hydrogen-bond-mediated aglycone delivery (HAD), we report herein the introduction of Picoloyl at C-4 and C-7 on thiosialyl donors. We also report the testing of the corresponding sialyl donors in several sialylation reactions, to elucidate the hypothesis of a Hydrogen-bond-mediated aglycone delivery (HAD) mechanism. However, exceptionally high stereoselectivities, yields and decreased reaction times were observed in the presence of an excess of triflic acid as a co-promoter.