正交设计法优化胸腺五肽固相合成工艺

Study on the solid-phase synthesis craft for thymopentin with orthogonal design

【目的】寻找固相合成胸腺五肽的较优工艺条件。【方法】采用Fmoc保护策略固相合成胸腺五肽,应用正交设计试验法,选取7种因素,每个因素选取2个水平,用高效液相色谱法确定生成物中胸腺五肽的产率,考察产率这一指标。【结果】胸腺五肽较优的合成条件为:氨基酸的用量比为1:3、哌啶的浓度为20%、脱保护基时间为30 min、缩合剂DCC与HOBt的用量比为2:1、缩合时间为6 h、裂解剂TFA的浓度为95%、裂解时间为30 min。哌啶的浓度、缩合剂DCC与HOBt的用量比、氨基酸的用量比为影响反应的主要因素。合成产率可达到38.4%。【结论】该合成工艺操作简便、周期短、产率较高、经济可行。

[Objective] To find out a best craft for thymopentin （TP-5） synthesis. [Methods] Fmoc strategy solidphase was used to synthesize TP-5. Applying orthogonal design, 7 factors were chosen and for each factor 2 levels were chosen. HPLC was used to determine the productive rate. [Results] Experimental factors： amino acids was 1： 3; piperdine was 20%; deprotective time was 30 min; DCC vs HOBt was 2： 1; condensation time was 6 hour; TFA was 95%; cracking time was 30 min. peperdine, DCC vs HOBt, and amino acids has main factors of this synthesis. Its yield reached 38.4%. [Conclusion] This craft is convenient for operation, short period, high yield and economical feasibility.