Intermolecular Phosphoryl Transfer Reaction

About more than ten years, Professor Yu-fen Zhao, the member of CAS studied systemically the chemical activity of twenty natural N-diisopropyloxyphosphoryl amino acids (DIPP-aa), and got plentiful and substantial achievements. DIPP-aa that was presented in water-alcohol tended to self-activate to give peptides, esters, phosphoryl esterification and N→O migration of the phosphoryl group, and it was known by us as the basic property of DIPP-aa. Also, it's interesting to study reactions of DIPP-aa further.In this paper, based on a lot of experiments, we found phosphoryl group could transfer from aat to aa2 when N-diisopropyloxyphosphoryl amino acid (DIPP-aai) reacted with another amino acids(aa2), that is to say, phosphoryl group could give intermolecular phosphoryl transfer reaction between two amino acids. The study could be divided three parts.The first part: the primary finding of phosphoryl transfer reaction. In this part, When we used the reaction of 0,0-phenylene phosphoryl O- trimethylsilyl serine trimethylsilyl ester and N,N-bis(trimethylsilyl) histidine trimethylsilyl ester and prepared seryl-histidine dipeptide, with the assistance, of HPLC-ESI-MS/MS, we found for the first time, there was almost equimolar amount of histidyl-histidine dipeptide in product as well as seryl-histidine dipeptide. The mechanism was speculated that there was phosphoryl transfer reaction between penta-coordinated phosphoryl serine and histidine in the reaction process. As a result, two types of dipeptide were produced.The second part: Based on a series of experiments, we found the extent of phosphoryl transfer reaction was much higher when DIPP-Ser protected by HMDS reacted with histidine protected by NMDS. Detected by ESI-MS, it was found that after phosphoryl group transfer from serine to histidine, histidine had self-assembled into His-His, His-His-His, His-His-His-His, respectively. Structures of these peptides were further confirmed by ESI-MS/MS.The third part: the generalizing of phosphoryl transfer reaction. According to the former study, we enlarged the range of research from serine and histidine to another amino acids. The result indicated basicity of amino acids was a vital factor for this kind of phosphoryl transfer reactions. With regard to the reaction of DIPP-aa1 and aa2, when basicity of aa2 was stronger than that of aa1, phosphoryl transfer could comeinto being; when basicity of aa2 was lower than that of aa1, phosphoryl transfer couldn't occur. In order to confirm this rule further, as a non-amino acid compound, hexamethylene diamine which has stronger basicity than any amino acids was used to react with DIPP-His in the same reaction condition as before. As we expected, because of the strong basicity of hexamethylene diamine, phosphoryl group could transfer quickly from histidine to it.