Formation of carboxamides with N,N,N′,N′-tetramethyl (succinimido) uronium tetrafluoroborate in aqueous / organic solvent systems

Synthesis of oligosaccharides with oligoethylene glycolspacers and their conversion into glycoconjugates usingN,N,N ? ,N ? -tetramethyl(succinimido)u roniu mtetrafluoroborate as coupling reagent

“…have demonstrated the use of TSTU as an efficient reagent for the formation of carboxamides from carboxytic acids. The reagent is compatible with an aqueous solvent system, but activation in N,N-dimethylformamide (DMF) was more efficient [9,10]. To dissolve hydrophilic, unprotected oligosaccharides the use of water as solvent is often a necessity and always an advantage.…”

“…Both the formation of the active ester and the conversion of this into the glycoconjugate could be monitored by TLC (EtOAc:MeOH:HOAc:H20, 12:3:3:1 by vot) and were found to be rapid and efficient. Slight modification of the published procedure [10] was necessary to achieve a high conversion into the intermediate active ester. Thus, lower yields were observed if an excess of base was used in the active ester formation.…”

“…General procedure for the synthesis of the deacylated spacer glycosides [8][9][10][11] The acetylated glycoside (100mg, 0.16-0.19mmol) was dissolved in ethanol (5 ml) and deacetylation was accomplished by addition of 0.25M sodium hydroxide (4 ml) and stirring at room temperature for 1 h. Neutralization with Dowex H + resins, filtration and concentration afforded the desired products 8-11 in quantitative yields. (8) -3,6,9,12-tetraoxatetradecanoic acid (9).…”

“…(8) -3,6,9,12-tetraoxatetradecanoic acid (9). (10) -3,6,9,12-tetraoxatetradecanamide (12) N,N,N',N"-Tetramethyl(succinimido)uronium tetrafluoroborate (TSTU) (59 mg, 0.20 mmol) was added at room temperature to a stirred solution of 9 (51 mg, 0.12 retool) and triethylamine (17.1 gt, 0.12 retool) in 2 ml dioxane:water (4:1 by vot). After 10 rain, the reaction mixture was added to a solution of pentylamine hydrochloride (0.15 retool) in 0.5M borate buffer (1 ml, pH 8.5).…”

“…We now report that N,N,N',N".tetramethyl(succinimido)uronium tetrafluoroborate (TSTU), shown to be a good reagent for the formation of carboxamides [9,10], efficiently transforms carboxylic acid spacer oligosaccharide derivatives into active esters and glycoconjugates. * This paper was first published in Glycoconfltgate Journal 10:197-201.…”