Oxidative Deamination of N-Acetyl Neuraminic Acid: Substituent Effects and Mechanism.

A study of the mechanism of the oxidative deamination of the N-nitroso-N-acetyl sialyl glycosides leading with overall retention of configuration to the corresponding 2-keto-3-deoxy-D-glycero-D-galacto-nonulopyranosidonic acid (KDN) glycosides is described, making use of a series of differentially O-protected N-nitroso-N-acetyl sialyl glycosides and of isotopic labeling studies. No evidence is found for stereodirecting participation by ester groups at the 4- and 7-positions. Comparisons are drawn with oxidative deamination reactions of 4-amino-4-deoxy and 2-amino-2-deoxy hexopyranosides and a common mechanism is formulated involving the intermediacy of 1-oxabicyclo[3.1.0]hexyl oxonium ions following participation by the pyranoside ring oxygen. A minor reaction pathway has been uncovered by labeling studies in the β-thiosialosides that results in the exchange of the 4-O-acetyl group by the glacial acetic acid that serves as external nucleophile in the general oxidative deamination process. A mechanism is proposed for this exchange involving participation by the thioglycoside at the level of an intermediate diazoalkane.