OSMAC-Driven Discovery of Six New Alkaloids from the Cold-Seep-Derived Fungus Talaromyces amestolkiae HDN21-0307

Six new alkaloid compounds, including two rare aromatic nitrile compounds talaronitriles A-B (<b>1</b>-<b>2</b>), a novel oxime-functionalized azadiphilone analogue talarooxime A (<b>3</b>), a new phenylhydrazone alkaloid talarohydrazone E (<b>4</b>), and two new dipeptide compounds talarodipeptides A-B (<b>5</b>-<b>6</b>), were isolated from the deep-sea cold-seep-derived fungus <i>Talaromyces amestolkiae</i> HDN21-0307 via OSMAC approach. Compound <b>1</b> is the first natural naphthalene compound with cyano groups. Compound <b>3</b> represents the first natural product containing an oxime-functionalized azadiphilone scaffold. Their structures and absolute configurations were elucidated through spectroscopic data analysis and quantum chemical calculations. Notably, compound <b>3</b> demonstrated moderate DPPH free-radical-scavenging activity, with an IC₅₀ value of 29.41 μM.