环六肽Thermoactinoamide A的固相合成及其抗菌活性

采用固相-液相两步法合成一种天然抗菌环肽Thermoactinoamide A。在9-芴甲氧羰基(Fmoc)固相合成的基础上,通过优化N,N-二异丙基乙胺(DIPEA)的添加量,得到直链肽,收率为84%,在此基础上,采用液相环合的方法对直链肽进行环合,通过优化环合体系中混合液的配比、初始pH等条件,得到Thermoactinomide A,收率为51%,总收率43%。抑菌实验结果表明,Thermoactinoamide A对金黄色葡萄球菌的最小抑菌浓度为32μg/mL。固相合成与液相环合两步法合成步骤少、过程简单、产率较高,为进一步研究该天然产物的生物活性及构效关系奠定了基础。

Solid-Phase Synthesis of Cyclohexapeptide Thermoactinoamide A and Its Antibacterial Activity

A natural antibacterial cyclic peptide thermoactinoamide A was synthesized by solid-liquid phase two-step method. First, based on fluorenylmethoxycarbonyl(Fmoc) solid phase synthesis, the linear peptide was obtained in 84% yield by optimizing the addition of N,N'-diisopropylethylamine(DIPEA). Then the linear peptide was converted to thermoactinoamide A in 51% yield(43% yield total) through optimizing the cyclization conditions. Antibacterial activity test results show that minimum inhibitory concentration of cyclic thermoactinoamide A for Staphylococcus aureus is 32 μg/mL. In summary, an effectively synthetic strategy was developed for further applications of cyclic peptide thermoactinoamide A on analyzing the structure-activity relationship and improving the bioactivity.