Efficient Large Scale Syntheses of 3‑Deoxy‑d‑manno-2-octulosonic acid (Kdo) and Its Derivatives

An efficient method to rapidly synthesize 3-deoxy-d-manno-2-octulosonic acid (Kdo) and its derivatives in large scale has been developed. Starting from d-mannose, the di-O-isopropylidene derivative of Kdo ethyl ester was prepared in three steps on a scale of more than 40 g in one batch in an overall yield of 75–80% without any intermediate purification. Kdo, Kdo glycal, and 2-acetylated Kdo ester were synthesized quickly in high yield from a di-O-isopropylidene derivative of Kdo ethyl ester. 2-Deoxy-β-Kdo ester was obtained with high stereoselectivity via the epimerization of the α-isomer using t-BuOH as a proton source.