【摘要】 以伐普肽为研究对象,用固相合成方法,并对偶合反应进行微波强化。利用正交实验研究了微波强化对偶合反应的促进作用。正交实验结果用多元非线性回归分析和响应面法优化,确定优化条件为:反应时间5min,包括1min升温、4min维持,最高反应温度60℃。与常规偶合反应相比,提高反应效率12~36倍。常规接肽反应保护氨基酸用量与固相合成树脂摩尔数之比为3倍,在优化的微波强化反应条件下,保护氨基酸用量减少为过量1倍;保护氨基酸与树脂的偶合效率明显提高,伐普肽得率从常规合成的48%提高到76%。其结构经质谱、高分辨质谱、红外光谱、核磁共振氢谱证实,与目标化合物的结构一致。更多还原

【Abstract】 Vapreotide was prepared by solid-phase peptide synthesis and effect of microwave on the coupling reaction was investigated by orthogonal test.Results were analyzed by multiple nonlinear regression method and response surface optimization.The optimal coupling reaction conditions were:maximum reaction temperature 60 ℃ and reaction time 5 min,including 1 min for raising the temperature and 4 min for maintaining.Compared with the conventional method,the microwave-enhanced coupling reaction time was shortened about 12～36 times and less amounts of protected amino acids were needed.The yield of vapreotide was increased from 48% to 76%.It was identified by ~1HNMR,IR,MS and HRMS,and the results were consistent with the proposed structure.更多还原