鳖甲活性寡肽I-C-F-6的合成工艺研究

Study on the synthetic process of active oligopeptide I-C-F-6 from Carapax trionycis

目的对I-C-F-6的固相合成工艺进行系统研究。方法以树脂类型、缩合剂类型、反应时间和投料比为考察因素进行L 9(34)正交实验设计,以相对含量为考察指标,优选合成工艺,并进行工艺验证和工艺放大研究。结果确定合成I-C-F-6的最佳工艺:用Fmoc-Gly-Wang树脂,以6-氯苯并三氮唑-1,1,3,3-四甲基脲六氟磷酸酯[O-(6-chloro-1-hydrocibenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphat,HCTU]N,N-二异丙基乙胺(N,N-diisopropylethylamine,DIPEA)为缩合剂,以1∶5为投料比反应2 h。以此工艺制备的I-C-F-6目标肽产率达77.03%,验证实验重复性好,5倍和25倍放大实验中目标肽的产率分别为62.86%和78.69%。结论建立的I-C-F-6合成工艺产率较高,重复性好,可为进一步的新药研究奠定基础。

Objective To study the solid-phase synthesis process of I-C-F-6 systematicly.Methods The synthetic process was optimized by using L 9(34)orthogonal experiment design,with the resin type,condensing agent type,reaction time,and feed ratio as the factors and the relative content as the investigation index.Under the optimized conditions,the synthetic process was verified and amplified.Results The optimized conditions were as follows:Fmoc-Gly-Wang resin as the resin,O-(6-chloro-1-hydrocibenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphat(HCTU)/N,N-diisopropylethylamine(DIPEA)as the condensing agent,and the feed ratio 1∶5 for 2 hours.Under the optimized conditions,the yield of the target peptide reached up to 77.03%.The yields of the target peptide in the 5 folds and 25 folds magnification experiments were 62.86%and 78.69%,respectively.Conclusion The synthetic process established has high yields and good repeatability,which lays a foundation for further research and development.