环（组氨酸-脯氨酸）二肽的高温高压辅助合成工艺优化

将高温高压技术应用于环（组氨酸-脯氨酸）二肽（cyclo(His-Pro)，CHP）的制备。以二肽甲酯盐酸盐为原料，采用高温高压辅助环化法在水中制备CHP，通过单因素试验考察了各种反应变量如压力、时间、溶液pH值以及底物质量浓度对CHP产率的影响，采用正交试验对高温高压辅助环化工艺条件进行优化。采用超高效液相色谱法和电喷雾质谱技术对产物中的CHP进行定量和定性分析。结果表明，最佳的反应条件为：反应压力0.20 MPa、反应时间3.5 h、溶液pH 6.0、底物质量浓度15 mg/mL。在此条件下可以得到较高产率（91.35%）的CHP，并且反应中没有观察到消旋。与传统的甲醇回流法相比，本研究的环化方法省时、高效、环保，并且能够得到较高的产率，同时产物没有发生消旋。

Optimization of High Pressure/Temperature Assisted Synthesis of Cyclo(His-Pro)

In this study the synthesis of cyclo(His-Pro) was investigated under high pressure/temperature condition. Using
dipeptide methyl ester hydrochloride as starting material, cyclo(His-Pro) was synthesized in water by high pressure/
temperature assisted cyclization. Influences of different reaction variables including pressure, time, solution pH and substrate
concentration on the yield of cyclo(His-Pro) were investigated by single-factor experiments, and then an orthogonal array
design was used to optimize the cyclization conditions. Quantification and identification of cyclo(His-Pro) in the product
were carried out by ultra performance liquid chromatography (UPLC) and electro spray ionization mass spectrometry
(ESI-MS). The optimum cyclization conditions were determined as follows: reaction pressure, 0.20 MPa; reaction time,
3.5 h; solution pH, 6.0; and substrate concentration, 15 mg/mL. Under such conditions, cyclo(His-Pro) was obtained in
excellent yield (91.35%) and no racemization was observed in the reaction process. In contrast to the classic methanol-reflux
cyclization, this method is rapid, environmentally friendly and highly efficient.