Acylated amino acids titration

Ohta, A., Toda, K., Morimoto, Y. et al. (2008) Effect of the side chain of A-acyl amino, acid surfactants on micelle formation an isothermal titration calorimetry study. Colloids Surf. A, 317, 316-322. 

It is difficult to anticipate all possible imperfections of the chain-building process and even more problematic to find perfect remedies for undesired side reactions. Therefore, one has to resort to monitoring the completion of the individual steps. Titration of unblocked amino groups with a strong acid, for instance perchloric acid, has been proposed as a method by which the process of deprotection and the progress of acylation can be followed. In acylation with active esters the absorption of the eliminated material (e.g. / -nitrophenol) in the ultraviolet can be used for monitoxing. Esters of 3-hydroxy-3,4-dihydro-l,2,3-... 

Reduction of 9-azido-NeuAc (3) with H2/PdO in acidic aqueous methanol affords 9-amino-NeuAc quantitatively. Acylation of 9-amino-NeuAc with NHS esters of various carboxylic acids at basic conditions (pH 8-9) readily affords various 9-substituted NeuAc derivatives in the yields ranging from 45% to 25%. To the solution of 3 in aqueous methanol, PdO was added and stirred under Ha atmosphere with pH maintained at 1-2 by addition of acetic acid. The reaction mixture was filtered to remove the catalyst when it was complete as determined by TLC. To the titrate was added dioxane, and 4-azidobenzoic acid NHS ester with pH maintained between 8.0-9.0 with saturated sodium bicarbonate solution. The mixture was stirred in the dark for 48 hr. The solvent was evaporated and the residue was purified by flash chromatography to give 4 in 45% yield. Rf ... 

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