大规模制备奥曲肽

Large Scale Synthesis of Octreotide

优化并放大了奥曲肽的合成技术。通过提高反应温度到40℃和选择弱极性溶剂二氯甲烷,将Fmoc-Thr(tBu)-O l与2-氯三苯甲基氯树脂的取代度提高到0.503 mmol/g。采用w(H2O2)=30%的水溶液合成二硫键,简化了分离氧化剂的步骤。自制10 g级大规模反应器,集成过滤、搅拌、控温、鼓泡四重功能,且操作方便。合成规模被放大到10 g水平,奥曲肽的产率从31.8%提高到48.7%,合成成本从1 000元/g降低为359元/g。

The synthesis technique of octreotide was optimized and magnified. The substitution degree of Fmoc-Thr（tBu）-O1 linked to 2-chlorotrityl chloride resin was improved to 0. 503 mmol/g by increasing the reaction temperature to 40 ℃ and choosing poorly polar solvent such as dichloromethane. The separation of oxidant was simplified by using 30% H202 in water to formate the disulfide bond. In selfdesigned 10 g-scale reactor, the four functions of filtration, agitation, temperature control and bubbling were combined, and manipulation of it was easy. The synthesis scale was magnified to the level of 10 g, as a result,the yield of octreotide was increased to 48.7% from 31.8% , and the cost was reduced to 359 RMB/g from 1 000 RMB/g.