Paecilosetin Derivatives as Potent Antimicrobial Agents from Isaria farinosa

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Fifty-seven entomopathogenic microorganisms were screened against human pathogens and subjected to mass spectrometry molecular networking based dereplication. Isaria farinosa BSNB-1250, shown to produce potentially novel biologically active metabolites, was grown on a large scale on potato dextrose agar, and paecilosetin ( 1 ) and five new analogues ( 2 – 6 ) were subsequently isolated. The structures of the new compounds were elucidated using 1D and 2D NMR. The absolute configurations of compounds 1 – 6 were determined using Mosher ester derivatives ( 1, 3, 4 ), comparison of experimental and calculated ECD spectra ( 2 – 4 and 6 ), and single-crystal X-ray diffraction analysis ( 5 ). Compounds 1 and 5 exhibited strong antibacterial activity against MSSA and MRSA with MIC values of 1–2 μg/mL.