Self-Assembly Of Amino Acids Into Peptides With Assistance Of Organic Phosphorus And Corresponding Mechanism

Phosphate esters and anhydrides play important roles in the biosynthesis of proteins, they act as the activators and carriers of amino acids in the biochemical reactions, and go away as the leaving groups after the formation of peptide bond. It is of signification to study further the prebiotic synthesis of polypeptides, the biosynthesis of proteins and application in the synthesis of polypeptides using organic phosphorus as the activating reagents of amino acids. In present dissertation, self-assembly of amino acids into peptides mediated by organic phosphorus and the corresponding mechanism were studied by using NMR, FAB-MS and HPLC techniques, some important results were obtained as follows:The trimethylsilyl derivatives ofα-amino acids, mediated by o-phenylene phosphorochloridate, could self-assemble into polypeptides and O-phosphoryl peptides. The mechanism went through sequential steps, i.e., the activation of amino acid, the elongation of peptide chain and the termination of the chain reaction. The activated amino acids were five-membered cyclic imino(alkyl)acetoxyphosphoranes. It is worth noting that only the N,O-bis(trimethylsilyl)-α-amino acids, not the N,O-bis(trimethylsilyl)-β-amino acids, could be activated and assemble into polypeptides. The mechanism of the five-membered cyclic imino(alkyl)acetoxyphosphorane intermediates showed that phosphorus could chooseα-amino acids in the prebiotic synthesis of polypeptides and the biosynthsis of proteins.When trimethylsilyl derivatives of more than two amino acids were mediated by o-phenylene phosphorochloridate, a series of heterogeneous polypeptides could be obtained. When ones of serine and threonine were involved, the O-phosphoryl peptides were found. This method may provide a novel synthetic strategy for the building of combinatorial peptide library. Some stable imino(alkyl)acetoxyphosphoranes were successfully synthesized. This method with the advantages of easy operation, rapid reaction rates and high yields, might provide two new routes for synthesis of other phosphoranes. The NMR analysis showed that the pseudorotation of these phosphoranes at room temperature was frozen. The mass spectral fragmentation pathways of these compounds were investigated by field desorption, electron impact and chemical ionization mass spectrometries.N-phosphopeptide analogues, N-phosphoamino esters, phosphodiesters and some products of ester exchange were obtained by reactions of imino(alkyl)-acetoxyphosphoranes with amines or alcohols. These results provided the evidence that the formation of imino(alkyl)acetoxyphosphorane intermediates was crucial to bioorganic reactions of N-phosphoamino acids.