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.

Metal Template Assisted Proximal Arrangement of a Nucleophile and an Electrophile: Site-Selective Acylation of α-Hydroxyamides in Polyols.

Site-selective acylation of α-hydroxyl groups in amides has been achieved in the presence of other primary hydroxyl groups with intrinsic high reactivity. In this methodology, a relatively stable pyridine aldoxime ester was exploited as an acyl donor to suppress undesired acylation. The catalytic activation of a pyridine aldoxime ester with a Lewis acid produced a cationic complex, which preferentially attracted the Lewis basic α-hydroxyamide via a template effect, to thus facilitate o-acylation.