Penipyridones A–F, Pyridone Alkaloids from Penicillium funiculosum

Six new pyridone alkaloids, named penipyridones A–F (1–6), were isolated from the fermentation broth of an Antarctic moss-derived fungus, Penicillium funiculosum GWT2-24. Their structures were elucidated from extensive NMR and MS data. Although they possess the same major chromophore and some of them presented almost mirror ECD spectra, their absolute configurations were found to be uniformly S, as evidenced by X-ray single-crystal diffraction analysis, stereocontrolled total synthesis, and chemical conversions. TDDFT-ECD calculations of compounds 3 and 6 revealed that subtle conformational changes are responsible for the significantly different ECD curves. None of the compounds were cytotoxic (IC₅₀ > 50 μM), while compounds 1, 2, 5, and 7 elicited lipid-lowering activity in HepG2 hepatocytes.