Integrating Molecular Networking and 1H NMR To Target the Isolation of Chrysogeamides from a Library of Marine-Derived Penicillium Fungi

A challenging problem in natural product discovery is to rapidly dereplicate known compounds and expose novel ones from complicated components. Herein, integrating the LC-MS/MS-dependent molecular networking and 1 H NMR techniques efficiently and successfully enabled the targeted identification of seven new cyclohexadepsipeptides, chrysogeamides A–G ( 1 – 7 ), from the coral-derived fungus Penicillium chrysogenum (CHNSCLM-0003) which was targeted from a library of marine-derived Penicillium fungi. Compound 4 features a rare 3-hydroxy-4-methylhexanoic acid (HMHA) moiety which was first discovered from marine-derived organisms. Interestingly, isotope-labeling feeding experiments confirmed that 13 C 1 - l -Leu was transformed into 13 C 1 - d -Leu moiety, indicating that d -Leu could be isomerized from l -Leu. Compounds 1 and 2 obviously promoted angiogenesis in zebrafish at 1.0 μg/mL with nontoxic to embryonic zebrafish at 100 μg/mL. Combining molecular networking with 1 H NMR as a discovery tool will be implemented as a systematic strategy, not only for known compounds dereplication but also for untapped reservoir discovery.