Site-Selective Acylations of α- and ß-Hydroxyamides in Complex Molecules: Application of Template-Driven Acylation to Disaccharides and a Glycopeptide.

Site-selective acylations of α-and ß-hydroxyamides in complex polyols are described. The combination of a pyridine aldoxime ester and Zn(OTf)2 facilitates the acylation of two types of N-glycolyl disaccharides, namely, Gal-GlcNGc and Neu5Gc-Gal, both of which are partial structures of polysaccharides responsible for biological actions, with highly site-selective modifications achieved. Furthermore, biotinylation, one of the most important techniques in chemical biology, is used to site-selectively acylate the ß-hydroxyl group in a glycopeptide.

Site-Selective Esterifications of Polyol ß-Hydroxyamides and Applications to Serine-Selective Glycopeptide Modifications.

The site-selective acylations of ß-hydroxyamides in the presence of other hydroxyl groups are described. Central to the success of this modification is the metal-template-driven acylation using pyridine ketoxime esters as acylating reagents in combination with CuOTf. This strategy enables ß-hydroxyl groups to be site-selectively acylated in various derivatives, including sterically hindered secondary ß-alcohol. The utility of this methodology is showcased by the serine-selective modification of a glycopeptide with unprotected sugar.