Pyridoneimine-catalyzed anomeric aqueous oxa-Michael additions of native mono- and disaccharides

A pyridoneimine-catalyzed oxa-Michael addition of protecting groups-free, native mono- and disaccharides with Michael acceptors in aq. solution is reported. Several mono- and disaccharides are reacted with acceptors, namely, methylvinyl ketone, acrylonitrile and tert-butyl acrylate in aq. solution, the addition catalyzed by npentylpyridone imine. The addition occurs site-selectively at the anomeric lactol and the remaining hydroxy functionalities are un-affected. The resulting keto-glycopyranoside products are explored in aldol, allylation and oxime product formation, occurring at either alpha-methyl moiety or at the keto-moiety, with appropriate synthons. In another direction, the keto-glycopyranoside is functionalized further with amino acids through reductive amination in aq. methanol solution. Formation of hemiacetal anion occurs in the presence of pyridoneimine in aq. Solution, enabling subsequent addition to occur with acceptors. Facile reductive amination of the resulting keto-glycoside provides an avenue for conjugations with amino acids in the present work.

Automated summary

This study reports a pyridoneimine-catalyzed oxa-Michael addition of protecting groups-free, native mono- and disaccharides with Michael acceptors in aqueous solution. The addition occurs with site-selectivity at the anomeric lactol, leading to the synthesis of keto-glycopyranoside products. These products can be further functionalized with amino acids through reductive amination. The method provides a facile way to conjugate mono- and disaccharides with amino acids.