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

Abstract

Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides, namely, asperversiamides A–C ( 1 – 3 ) and asperheptatides A–D ( 4 – 7 ) and an unusual pyrroloindoline-containing new cycloheptapeptide, asperpyrroindotide A ( 8 ). The structure of 8 was elucidated by comprehensive spectroscopic data analysis, and its absolute configuration was determined by advanced Marfey’s method. The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized. Additionally, a series of new derivatives ( 10 − 19 ) of asperversiamide A ( 1 ) was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra. The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.

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