Chemoenzymatic synthesis of ring 18O-labeled sialic acid

Abstract

Methyl 4,6-O-benzylidene-α-D-glucopyranoside was converted into methyl 2-azido-2-deoxy-4,6-O-benzylidene-α-D-altropyranoside via a synthetic route that incorporated two inversions of configuration. Activation of the C-3 hydroxyl group as a triflate ester followed by an SN2 reaction with O-18 labeled benzoate gave, after standard functional group manipulations, 2-acetamido-2-deoxy-D-(3-18O)mannose. Coupling of the labeled N-acetyl-mannosamine with pyruvate was catalyzed by sialic acid aldolase to give ring-oxygen-labeled sialic acid in an overall yield of 11.4% over 10 steps.Key words: N-acetylneuraminic acid, sialic acid oxygen-18, chemoenzymatic.