Clavatol derivatives from the endophytic fungus Penicillium commune XL-0473

Thirteen previously undescribed clavatol derivatives (1, 2, 3a, 3b, and 4−12), along with thirteen known compounds were isolated from the endophytic fungus Penicillium commune XL-0473. Their structures were established through comprehensive spectroscopic analyses, quantum chemical electronic circular dichroism calculations, single-crystal X-ray diffraction, and chemical synthesis experiment. Notably, compounds 1 and 2 represent the first reported clavatol dimers conjugated with amino acids. Compounds 8–11 are unprecedented derivatives containing a 1,6-dioxaspiro[4.4]nonane framework. Compound 16 demonstrated potent antibacterial activity against multidrug-resistant pathogens, with MIC values ranging from 3.13 to 6.25 μg/mL. A plausible nonenzymatic self-assembly mechanism involving ortho-quinone methide intermediates was proposed to explain their biosynthesis pathway.