Targeted Isolation of Asperheptatides from a Coral-Derived Fungus Using LC-MS/MS-Based Molecular Networking and Antitubercular Activities of Modified Cinnamate Derivatives.
Chao R, Hou XM, Xu WF, Hai Y, Wei MY, Wang CY, Gu YC, Shao CL.
Under the guidance of MS/MS-based molecular networking, four new cycloheptapeptides, namely, asperheptatides A-D (<b>1</b>-<b>4</b>), were isolated together with three known analogues, asperversiamide A-C (<b>5</b>-<b>7</b>), from the coral-derived fungus <i>Aspergillus versicolor</i>. The planar structures of the two major compounds, asperheptatides A and B (<b>1</b> and <b>2</b>), 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 (<b>3</b> and <b>4</b>), were characterized by ESI-MS/MS fragmentation methods. A series of new derivatives (<b>8</b>-<b>26</b>) of asperversiamide A (<b>5</b>) were semisynthesized. The antitubercular activities of <b>1</b>, <b>2</b>, and <b>5</b>-<b>26</b> against <i>Mycobacterium tuberculosis</i> H37Ra were also evaluated. Compounds <b>9</b>, <b>13</b>, <b>23</b>, and <b>24</b> showed moderate activities with MIC values of 12.5 μM, representing a potential new class of antitubercular agents.