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 (-), were isolated together with three known analogues, asperversiamide A-C (-), from the coral-derived fungus . The planar structures of the two major compounds, asperheptatides A and B ( and ), 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 ( and ), were characterized by ESI-MS/MS fragmentation methods. A series of new derivatives (-) of asperversiamide A () were semisynthesized. The antitubercular activities of , , and - against H37Ra were also evaluated. Compounds , , , and showed moderate activities with MIC values of 12.5 μM, representing a potential new class of antitubercular agents.