Efficient Synthesis of 4-Amido-N5-acetyl-4-deoxyneuraminic Acid and Its Application to the C-4 Modification of Sialic Acids

A straightforward synthesis of 4-amido-N-6-acetyl-4-deoxyneuraminic acid, a key precursor to various 4-amidoneuraminic acid analogues, has been achieved using a highly regioselective and diastereoselective [3 + 2]-cycloaddition of D-mannose-derived nitrone with methyl acrylate. Advantages of this newly developed synthesis include the use of economically available materials and reagents, the ease of operations and the excellent control of stereochemistry, as well as the convenience in application to the C-4 modifications of sialic acids.