基于光敏感保护策略的Phakellistatin 13固相合成

发布时间：2018-07-04 09:30

本文选题：光敏感保护基 + 固相合成　；参考：《国际药学研究杂志》2015年02期

【摘要】：目的使用光敏感保护基和固相合成法制备Phakellistatin 13。方法使用二氢吡喃树脂作为固相载体,利用自行制备的光敏感保护基对苏氨酸进行保护并将其固定于树脂上。以该苏氨酸作为起始氨基酸,进行常规肽链组装,肽链组装完毕后通过光照脱去光敏感保护基,在固相上完成环合,切除后得到游离环肽。结果使用邻硝基乙苯一步制得了具有光敏感作用的2-(2-硝基苯基)-丙醇(Npp-OH),利用该保护基保护了苏氨酸羧基并借此完成了Phakellistatin 13的合成。终产物结构经高分辨质谱确证,表明该策略切实可行,为环肽的合成提供了有效的工具。结论 Npp保护基易于制备,保护和去保护收率高,对酸碱稳定,因此是一种优良的第三维保护基。利用该保护基,有效的完成了环肽的合成。
[Abstract]:Objective to prepare Phakellistatin 13 by photo-sensitive protective group and solid state synthesis. Methods using dihydropyran resin as solid phase carrier, the photo-sensitive protective group was used to protect threonine and immobilized on the resin. Threonine was used as the starting amino acid to assemble the peptide chain. After the assembly of the peptide chain, the photosensitive protective group was removed by light, the cyclization was completed on the solid phase, and the free cyclic peptide was obtained after removal. Results the photo-sensitive 2- (2-nitrophenyl) -propanol (Npp-OH) was prepared from o-nitroethylbenzene. The protective group was used to protect the threonine carboxyl group and Phakellistatin 13 was synthesized. The structure of the final product was confirmed by high resolution mass spectrometry, which shows that the strategy is feasible and provides an effective tool for the synthesis of cyclic peptides. Conclusion the NPP protection group is easy to be prepared, and has high yield of protection and deprotection, and is stable to acid and base, so it is a good third dimensional protective base. Using this protective group, the synthesis of cyclopeptide was effectively completed.
【作者单位】：北京工业大学生命科学与生物工程学院;军事医学科学院放射与辐射医学研究所;北京大学基础医学部;
【基金】：国家自然科学基金资助项目(81273431,81072531,30770655,21272273)
【分类号】：R914.5

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