A High Resolution MS, MS/MS Database Using LTQ-Orbitrap XL Mass Spectrometer Interfaced with H-ESI for Dereplication of Fungal Secondary Metabolites

In an ongoing anticancer drug discovery project, over 180 compounds have been isolated from filamentous fungi, with more than 30% of these being new to the literature. Since the isolation and purification of these compounds is tedious and costly, it is essential to discriminate between previously known and new compounds at the start of the discovery process. To achieve this goal, a 5-minute method for the dereplication of fungal secondary metabolites in crude culture extracts was developed utilizing a UPLC-PDA system interfaced with a heated electrospray ionization (H-ESI) source and coupled with an LTQ Orbitrap XL mass spectrometer. A spectral database consisting of HRMS and MS/MS data of natural products previously isolated and characterized by the group was created using this method. As hundreds of fungal cultures are being examined each year in our laboratory, this new dereplication method is twice as fast as the method reported previously and provides an efficient process for the prioritization of extracts that may yield interesting new compounds.