3-Hydroxy- N-acetylneuraminic acid: Synthesis and inhibitory properties

3-Hydroxy- N-acetylneuraminic acid was synthesized by the condensation of N-acetyl d-mannosamine with bromopyruvate or hydroxypyruvate in yields of 24.4 and 12.7%, respectively. The product was characterized by its infrared and nuclear magnetic resonance spectra, thin-layer chromatography, optical rotation, neutralization equivalent and direct Ehrlich chromogen. This substituted sialic acid was a weak noncompetitive inhibitor of N-acetyl neuraminic acid aldolase purified from Clostridium perfringens. The inhibitor had a K i of 75 m m and a minimum inactivation halftime of 0.80 min. Hydroxypyruvate was an effective noncompetitive inhibitor of the aldolase with a K i of 0.70 m m. The mechanism of inhibition and possible reasons for the difference between the effectiveness of hydroxypyruvate and 3-hydroxy- N acetylneuraminic acid as noncompetitive inhibitors are discussed.