Solution phase synthesis of amide-linked N-acetyl neuraminic acid, alpha-amino acid, and sugar amino acid conjugates

Peracetylated N-acetylneuraminic acid (NeuAc) was efficiently coupled to esters of glycine, alanine, and serine using BOP and HOBT in the presence of DIEA. Deprotection of the esters readied the NeuAc-alpha-amino acid conjugates for further elaboration. Coupling of the NeuAc-gly adduct with beta-O-methoxy neuraminic acid methyl ester afforded a selectively protected glycine linked sialic acid dimer. 2-Amino-3,4-di-O-benzyl-(1-->6)-anhydroglucose and alanine benzyl ester were also efficiently coupled to the bis adduct giving novel trimeric analogs. Elimination of the anomeric acetate from the NeuAc-gly dimer followed by global deprotection provided a novel saccharopeptide with modest clostridial sialidase inhibitory activity.