Direct sialic acid 4-OAc substitution by nitrogen, sulfur and carbon nucleophiles with retention of stereochemistry

A direct one-step nucleophilic substitution of the 4-OAc of acetyl protected Neu5Ac is presented. Previously published methods for direct substitution of the 4-OAc are limited to cyclic secondary amines. Here we present conditions that allow for a much wider range of nitrogen nucleophiles as well as thiols and cyanide, to be used. The present investigation significantly broadens the scope of 4-aminations and allows for the introduction of a wide variety of different nucleophiles.