Synthesis of protein conjugates and analogues of N-acetylneuraminic acid

Abstract

R E N~ ROY and CRAIG A. LAFERRI~RE. Can. J. Chem. 68, 2045Chem. 68, (1990. N-Acetylneuraminic acid (I) was prepared from the salivary gland mucins of the Chinese swiftlet by an improved procedure using acidic resin hydrolysis. Compound 1 was transformed into the known acetochloroneuraminic acid (3) by a new two-step procedure. Koenigs-Knorr glycosylation of 3 followed by subsequent reductive ozonolysis of the 2-propenyl a-glycoside afforded the key aldehyde precursors 7 and 8, which were coupled to bovine serum albumin or tetanus toxoid by reductive amination. The factors influencing the extent of incorporation were investigated. A series of N-acetylneuraminic acid analogues modified at strategic functionalities were also synthesized.

Accessibility of N-acyl-d-mannosamines to N-acetyl-d-neuraminic acid aldolase

“…Direct hydrolysis of NeuNAc under either acidic or basic conditions caused its decomposition probably due to the involvement of its keto α-hydrogens in the open chain form. Therefore, NeuNAc (1) was first converted into the benzyl glycoside 20 [28][29][30] that could be hydrolyzed under basic conditions smoothly to afford 21. Selective acylation of the free amino group of 21 using various acyl anhydrides or the active ester of trifluoropropionic acid was followed by catalytic debenzylation to give N-acylsialic acids 11-18.…”

Preparation and immunological studies of protein conjugates of N-acylneuraminic acids

“…To a solution of 21 [31] (200 mg, 0.54 mmol) in water (5 mL) was added 5 mL of 20% tetramethylammonium hydroxide in MeOH (20% w/w). After the reaction mixture was refluxed for 6 h, it was neutralized with concentrated HCl and then condensed to dryness under reduced pressure.…”

“…The reactions to prepare 21 were well established [31]. The deacetylation of 21 was achieved by refluxing its aqueous methanol solution in the presence of tetramethylammonium hydroxide.…”

Base- and Sugar-Modified Cytidine MonophosphateN-Acetylneuraminic Acid (CMP-Neu5Ac) Analogues - Synthesis and Studies with α(2-6)-Sialyltransferase from Rat Liver

“…In order to cope with this situation, known allyl Neu5Ac derivative 40 [26] (Scheme 9) was selected as the starting material. Treatment of 40 with dimethoxytrityl chloride (DMTr-Cl) in pyridine in the presence of 4-dimethylaminopyridine (DMAP, Steglich reagent) afforded the 9-O-DMTr derivative, which gave compound 41 upon O-acetylation.…”

“…The combined organic layers were dried with magnesium sulfate and concentrated. To a solution of 40 [26] (1.4 g, 3.86 mmol) in dry pyridine (14 mL) was added 4-dimethylaminopyridine (94 mg, 0.771 mmol) and dimethoxytrityl chloride (1.56 g, 4.63 mmol) and the mixture was stirred overnight. Acetic anhydride (6 mL) was added and the mixture was stirred for a further 12 h. The mixture was concentrated and coevaporated with toluene.…”