Oxidative Deamination ofN-Acetyl Neuraminic Acid: Substituent Effects and Mechanism

Abstract

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 labelling 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 labelling 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.

Stereoselective Synthesis of 5-epi-α-Sialosides Related to the Pseudaminic Acid Glycosides. Reassessment of the Stereoselectivity of the 5-Azido-5-deacetamidosialyl Thioglycosides and Use of Triflate as Nucleophile in the Zbiral Deamination of Sialic Acids

“…Accordingly, 6 was converted to the N -nitroso derivative 7 by reaction with nitrosonium tetrafluoroborate in the presence of pyridine in dichloromethane at −10 °C as described previously 23,55 before exposure to sodium isopropoxide and trifluoroethanol in dichloromethane at −10 °C and subsequent addition of levulinic acid (Scheme 1). Work up and chromatographic purification then afforded the 5- O -levulinyl KDN derivative 8 in 49% yield together with the 4,5-di- O -levulinyl product 9 in 21% yield.…”

Synthesis and intramolecular glycosylation of sialyl mono-esters of o-xylylene glycol. The importance of donor configuration and nitrogen protecting groups on cyclization yield and selectivity; isolation and characterization of a N-sialyl acetamide indicative of participation by acetonitrile

“…Coupling with benzene-1,2-dimethanol by means of dicyclohexylcarbodiimide and N -hydroxybenzotriazole then afforded the ester 3 in 70% yield (Scheme 1). The anomer 4 21 of 1 was similarly converted to the corresponding acid 5 in 70% yield by treatment with lithium iodide in pyridine at reflux. Alternatively, 4 was saponified giving, after reinstallation of the acetyl groups, a 73% yield of the acid 5 that was converted to the ester 6 in 35% yield (Scheme 1).…”

“…Application of the lithium iodide demethylation and DCC re-esterification protocol to the N -acetyl-oxazolidione 17 and isothiocyanato 11 systems 7 and 10 then gave the esters 9 and 12 , via the acids 8 and 11 , in 53 and 43% overall yield, respectively (Scheme 1). In view of the relative inaccessibility of the equatorial thioglycoside 4 , 21 no attempt was made to prepare, or study the cyclization of the α-anomers of either 9 or 12 .…”

“…A mixture of 4 17,21 (0.10 g, 0.16 mmol) and anhydrous pyridine (1.4 mL) was added to anhydrous LiI (0.07 g, 0.56 mmol) under an argon atmosphere. The reaction mixture was heated to reflux for 4 h under an argon atmosphere before it was cooled to room temperature and concentrated to dryness under reduced pressure.…”

“…A solution of 4 17,21 (0.98 g, 1.52 mmol), methanol (9.8 mL) and 1N NaOH (19.5 mL) was stirred for 24 h, then co-evaporated with ethanol (×2) and toluene (×3). The crude residue was dissolved in pyridine (8.9 mL), treated with acetic anhydride (10.3 mL) at 0 °C, and stirred overnight at room temperature.…”