Malonates reaction with peptide

Further coupling of these derivatives with 2-substituted malonic acid monoester 13 using DCC-HOBt or reaction with Meldrum s acid derivatives 12 after in situ trimethylsilylation with excess N,0-bistrimethylsilyla-cetamide (BSA) gives the protected pseudodipeptide unit 28, which can be coupled to the growing peptide chain on a solid support (Scheme 10) [122]. 

Proteic materials used in traditional tempera painting, for instance, are subject to condensation and cross-linking reactions with other components such as lipids. Gas chromatography-mass spectrometry (GC-MS) investigations have shown that the oxidative degradation of amino acids such as cysteine, serine, and phenylalanine leads to the formation of amino malonic acid. The latter compound has been identified via the analysis of aged paint samples [7]. Other modifications are caused by the pH variation of the paint surface that contributes to the hydrolysis of peptide bonds and the partial dehydration of serine and threonine. 

Malonic acid serves as a ketene precursor in solid phase N-acetylation of peptides catalyzed by diisopropylethylamine by reaction with the catalyst HBTU (O-benzotriazole-iV, N, N, JV -tetramethyluronium hexafluoro-phosphate) in dg-DMF forming a malonate/tetramethylurea complex that gives ketene and tetramethylurea, as shown by anisidine acetylation (Scheme 4.7). Computational methods favored the pathway shown for ketene generation. This method was used in the acetylation of a variety of resin bound peptides. 

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