Pk(A) Modulation Of Pyrrolidine-Based Catalytic Polymers Used For The Preparation Of Glycosyl Hydrazides At Physiological Ph And Temperature

Inspired by the ability of enzymes to use the surrounding hydrophobic and/or polarizable groups to modulate the pKa of a given amino acid, we designed a series of soluble polymers able to decrease the basicity of pyrrolidine (from 11.2 to 8.6 pKa units), which clearly increases its aminocatalytic activity at physiological pH in C-N bond formation reactions via ion iminium activation. Other parameters such as charge density, hydrophobic/hydrophilic balance, and aggregation state have been studied as important factors in the catalytic activity of the polymers for a given substrate. To demonstrate the utility of our approach, an optimal pyrrolidine-based catalytic polymer has been used for the formation of CN bonds between hydrazides and free sugars as the model system for the preparation of glycoconjugates.