Expedient syntheses of neoglycoproteins using phase transfer catalysis and reductive amination as key reactions

Abstract

Starting from peracetylated chloro- or bromo-glycosyl donors of N-acetylneuraminic acid, N-acetylglucosamine, glucose and lactose, the corresponding p-formylphenyl glycosides were synthesized stereospecifically under phase transfer catalysed conditions at room temperature in yields of 38-67%. After Zemplén de-O-acetylation, the formyl groups were directly and chemoselectively coupled to the lysine residues of bovine serum albumin by reductive amination using sodium cyanoborohydride. The conjugation reactions were followed as a function of time and under a series of different molar ratios of the reactants to provide glycoconjugates of varying degree of antigenicities. Thus, carbohydrate protein conjugates were made readily available using essentially two key reactions.