Studies on preparation of amino acid active ester in peptide synthesis

The yield and purity of synthetic peptides were greatly affected by the activation reaction of amino acid.N-(9-Fluorenylmethoxycarbonyl)-valine was taken as an example to study the reaction of active ester of amino acids.The reaction was detected by reversed phase HPLC for the first time,and an analytical method for N-(9-fluorenylmethoxycarbonyl)-valine active ester was established.The reaction conditions for preparing this active ester were optimized,and tetrahydrofuran as the new solvent system was introduced for synthesis of peptide using Fmoc strategy.The experimental results indicated that solvents and active reagents had a remarkable effect on the yield of active ester.The best condition for preparing the active ester was a ratio of n(Fmoc-Val-OH)∶n(HOBt)∶n(DCC)=1∶1∶1.2,with THF used as the solvent at a temperature of 25 ℃,respectively.