基于光敏感保护策略的Phakellistatin 13固相合成  

Solid-phase synthesis of Phakellistatin 13 based on photolabile protecting strategy

作　　者：王刚[1,2] 彭涛[2] 张首国[2] 王君逸 温晓雪[2] 颜海燕[2] 胡利明[1] 王林[1,2] 

机构地区：[1]北京工业大学生命科学与生物工程学院,北京100022 [2]军事医学科学院放射与辐射医学研究所,北京100850 [3]北京大学基础医学部,北京100191

出　　处：《国际药学研究杂志》2015年第2期215-219,共5页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金资助项目(81273431,81072531,30770655,21272273)

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。Objective Preparation of the Phakellistatin 13 by using of solid-phase peptide synthesis method and photolabile protecting group. Methods By using of the DHP resin as the solid-phase supporter, a threonine derivative which was protected by the self-prepared photolabile protecting group was anchored to. The linear peptide was assembled via standard procedure with the threonine as the starting amino acid. After that, the photolabile protecting group was removed by UV irradiation, and the cyclization was completed while the peptide was still attached on the beads. The free cyclic peptide was then cut off by acid. Results The photolabile 2-（2-nitrophenyl）-propanol （Npp-OH） was synthesized in one step from o-nitroethylbenzene. With the Npp group, the earboxyl group of threonine was blocked and Phakellistatin 13 was synthesized. The Phakellistatin 13 was identified by high resolution mass spectrometry, indicated that the strategy is quite available, which offer an efficient method for cyclic peptide synthesis. Conclusion The Npp group had the advantages of easy prepared, high yields for protection and deprotection, be stable to the acidic and alkaline conditions, therefore it is an excellent third division protecting group. With this group, the cyclic peptide can be synthesized efficiently.

关 键 词：光敏感保护基 固相合成 Phakellistatin 13 

分 类 号：R914.5[医药卫生—药物化学]