使用基于液相色谱-串联质谱的分子网络技术，靶向分离抗结核环庚肽和一种含不寻常吡咯并吲哚啉的新类似物——曲霉吡咯吲哚肽A。

Targeted isolation of antitubercular cycloheptapeptides and an unusual pyrroloindoline-containing new analog, asperpyrroindotide A, using LC-MS/MS-based molecular networking.

作者信息

Han Yi-Qian, Zhang Qun, Xu Wei-Feng, Hai Yang, Chao Rong, Wang Cui-Fang, Hou Xue-Mei, Wei Mei-Yan, Gu Yu-Cheng, Wang Chang-Yun, Shao Chang-Lun

机构信息

Key Laboratory of Marine Drugs, the Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003 China.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004 China.

出版信息

Mar Life Sci Technol. 2023;5(1):85-93. doi: 10.1007/s42995-022-00157-8. Epub 2023 Jan 20.

UNLABELLED

Further insights on the secondary metabolites of a soft coral-derived fungus under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides, namely, asperversiamides A-C (-) and asperheptatides A-D (-) and an unusual pyrroloindoline-containing new cycloheptapeptide, asperpyrroindotide A (). The structure of was elucidated by comprehensive spectroscopic data analysis, and its absolute configuration was determined by advanced Marfey's method. The semisynthetic transformation of into was successfully achieved and the reaction conditions were optimized. Additionally, a series of new derivatives (-) of asperversiamide A () was semi-synthesized and their anti-tubercular activities were evaluated against H37Ra. The preliminary structure-activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s42995-022-00157-8.

未标注

在基于串联质谱的分子网络指导下，对一种源自软珊瑚的真菌的次生代谢产物有了进一步认识，从中分离出七种已知的环庚肽，即asperversiamides A - C（-）和asperheptatides A - D（-），以及一种含吡咯并吲哚啉的不寻常新环庚肽，asperpyrroindotide A（）。通过综合光谱数据分析阐明了其结构，并采用先进的马尔费方法确定了其绝对构型。成功实现了将转化为的半合成转化，并优化了反应条件。此外，半合成了一系列asperversiamide A（）的新衍生物（-），并评估了它们对H37Ra的抗结核活性。初步的构效关系表明，丝氨酸羟基和色氨酸残基对活性很重要。