Peptides, nitrosation

Commeyras and co-workers proposed for the first time a prebiotically relevant synthetic pathway [143,144]. They established that the nitrosation of N-carbamoylamino acids 25 (otherwise believed as unreactive in prebiotic environments) by nitrogen oxides (typically obtained by mixing O2 and NO) quantitatively releases NCA. Although first tested in organic solvent [ 143], the reaction proved to work in the solid state [144], and also in aqueous solution [145], where the NCA can be observed for ca. 1 h prior to its conversion into either free amino acids or peptides. 

Fig. 5 The Primary Pump, a peptide-based protometabolism scenario [146] involving the following steps I amino acid N-carbamoylation II concentration through drying III NO -mediated CAA activation IV dissolution through watering (by e.g. sea water) V NCA reaction in aqueous phase (Va NCA hydrolysis Vb condensation with AA or peptide) VI slow hydrolysis of peptide bonds VII a-carbon epimerization (Vila of amino acid and CAA VNb of peptide residues). Additional steps corresponding to peptide N-carbamoylation/nitrosation have not been mentioned for the sake of clarity. It is worth mentioning that although the N-carbamoylation of peptides renders them unre-active towards NCA, this is reverted by NOx-mediated nitrosation [197], thus keeping peptides within the polymerization process...

The reaction should lend itself in principle to fission of those peptides that are cleaved by nitrosating agents. 

Preparation of acyl azides by the nitrosation method has been used to advantage in the synthesis of peptides " (cf. section III.B.3) and is particularly valuable since it is the only procedure for peptide chain lengthening which does not cause racemization of the peptide components The use of acyl azides as protecting... 

Because of the deep interest of the chemistry of a-aminoacide-N-carboxyanhydrid es in peptide synthesis, many attempts have been imdertaken to develop an efficient method of obtaining these compounds. Nitrosation of N-carbamoyl-valine with the system NO/O yields the N-nitroso-N-carbamoyl-valine which decomposes into a-isocyanatoacid which is converted into the anhydride [38] ... 

The formamides are sufficiently, stable to find wide use, particularly in peptide synthesis. An important general method for preparing a-amino acids starts from a malonic ester and involves nitrosation, reductive formylation, and alkylation of the formamido-malonic ester (4) [27-29]. The corresponding acetamido [28, 20-32] and benzamido [33, 34] derivatives have also been used. In conventional peptide synthesis the formyl group has been used to protect oc-amino acids while coupling them to oc-amino esters [35]. Mild, selective hydrolysis... 

Meat preservative, reagent for peptide synth. and nitrosation. Chemical ionisation reagent used in mass spectrometry. Liq. Bp 78°, BP43 24-27°. 

Nitrosation of the indole nucleus was found to be a drawback in the synthesis of tryptophan peptides when the azide coupling procedure was used (see Section VI. 1. for more details). The nitrosation reaction has been also found useful in devising an analytical method for determination of tryptophan and related indole compounds (see Section IV.6.). 

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