Targeted Isolation of Asperheptatides from a Coral-Derived Fungus Using LC-MS/MS-Based Molecular Networking and Antitubercular Activities of Modified Cinnamate Derivatives

Under the guidance of MS/MS-based molecular networking, four new cycloheptapeptides, namely, asperheptatides A–D ( 1 – 4 ), were isolated together with three known analogues, asperversiamide A–C ( 5 – 7 ), from the coral-derived fungus Aspergillus versicolor . The planar structures of the two major compounds, asperheptatides A and B ( 1 and 2 ), were determined by comprehensive spectroscopic data analysis. The absolute configurations of the amino acid residues were determined by advanced Marfey’s method. The two structurally related trace metabolites, asperheptatides C and D ( 3 and 4 ), were characterized by ESI-MS/MS fragmentation methods. A series of new derivatives ( 8 – 26 ) of asperversiamide A ( 5 ) were semisynthesized. The antitubercular activities of 1, 2, and 5 – 26 against Mycobacterium tuberculosis H37Ra were also evaluated. Compounds 9, 13, 23, and 24 showed moderate activities with MIC values of 12.5 μM, representing a potential new class of antitubercular agents.