Active ester chemistry

A surface coated with a SAM of 3-mercaptoproponic-acid, was used for the covalent attachment of Alexa-Fluor 647 labeled streptavidin (AF-SA) by means of NHS-active ester chemistry [38]. This reaction yielded an SPR minimum shift of A0 O.27° and contributed a fluorescence intensity of A/A 350 eps (layer b ). Subsequently, the alternate binding of biotinylated IgG and streptavidin from 20 pg ml-1 solutions was monitored. 

In addition to the design principles just mentioned, peptides, proteins, and peptide-based supramolecular structures can be cross-linked into 3D networks via conventional synthetic chemistry (e.g., active ester chemistry or short synthetic cross-linkers) or via bioorthogonal click chemistry (e.g., Michael-type addition), utilizing their inherent multitude of functional groups (—NH, —COOH, —SH) and/or other additionally introduced functionalities. 

Scheme 12.8 Cyclization of polystyrene using activated ester chemistry (37).

Arshady, R. Polymer Synthesis via Activated Esters A New Dimension of Creativity in Macro-molecular Chemistry. VoL 111, pp, 1-42. 

B Liberek. The nitrile group in peptide chemistry. V. Racemization during peptide synthesis. 4. Racemization of active esters of phthaloyl-P-cyano-L-alanine in the presence of trie thy lamine. Acad Pol Sci Ser Sci Chim 11, 677, 1963. 

J Kovacs, R Cover, G Jham, Y Hsieh, T Kalas. Application of the additivity principle for prediction of rate constants in peptide chemistry. Further studies on the problem of racemization of peptide active esters, in R Walter, J Meienhofer, eds. Peptides Chemistry, Structure and Biology. Ann Arbor, MI, 1975, pp 317-324. 

M Jaouadi, C Selve, JR Dormoy, B Castro, J Martinez. Isopropenyl chloroformate in the chemistry of amino acids and peptides. III. Synthesis of active esters of A-protected amino acids. Tetrahedron Lett 26, 1721, 1985. 

The active ester methodology, which is widely used in peptide chemistry, has found only limited application in depsipeptide synthesis. A more vigorous activation of the carboxy component is apparently required to form an ester bond compared to the peptide analogue. Nevertheless, active esters have been utilized for this purpose in combination with some catalyst additives. The first successful attempt in this direction was described by Mazur.1103 The modification of the 4-nitrophenyl ester procedure included addition of 1-10 equivalents of imidazole to the reaction mixture. This accelerated technique presumably involves formation of the highly reactive intermediate imidazolide. The reaction resulted in the preparation of model benzyloxycarbonyl didepsipeptide esters in good yields within several hours at room temperature from 4-nitrophenyl esters of Z-amino acids and the pentamethylbenzyl ester of glycolic acid, while in the absence of imidazole this reaction failed to give any product. 

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