title: Preparative Scale MS-Guided Isolation of Bioactive Compounds Using High-Resolution Flash Chromatography: Antifungals from Chiloscyphus polyanthos as a Case Study.
abstract: In natural product research, the efficient purification of molecules from large amounts of complex extracts is a key element. In this regard, an integrative strategy for efficient MS-guided isolation of antifungal compounds has been developed. First, off-line HPLC antifungal activity-based profiling and HPLC-PDA-MS profiling were used to localize the compounds of interest on the analytical scale. Then, the analytical gradient was geometrically transferred to the flash chromatographic level. Finally, an MS-triggered isolation of the localized bioactive molecules was realized using high-resolution flash chromatographic columns (15 µm spherical particles) coupled to a single quadrupole mass spectrometer via a splitter system. This isolation strategy was applied for the MS-targeted purification of antifungal principles from the liverwort Chiloscyphus polyanthos. This rational methodology has high potential for the targeted large-scale purification of bioactive compounds, avoiding the need to repeat a given bioassay at each isolation step. Seven sesquiterpene lactones were isolated, of which five were found to be bioactive and one was reported as a new compound. The absolute configuration of some compounds was established for the first time by electronic circular dichroism spectroscopy.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Azzollini
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Favre-Godal
authors.affiliation: Department of Natural Products Chemistry, Key Lab of Chemical Biology of the Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of China.
authors.forename: Jiaozhen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
authors.forename: Samad Nejad
authors.initials: SN
authors.lastname: Ebrahimi
authors.affiliation: Department of Natural Products Chemistry, Key Lab of Chemical Biology of the Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of China.
authors.forename: Shuqi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Natural Products Chemistry, Key Lab of Chemical Biology of the Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Fan
authors.affiliation: Department of Natural Products Chemistry, Key Lab of Chemical Biology of the Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Davy
authors.initials: D
authors.lastname: Guillarme
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Emerson Ferreira
authors.initials: EF
authors.lastname: Queiroz
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Wolfender
mesh_terms: D000935:Antifungal Agents / Q000302:isolation & purification* / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D035926:Hepatophyta / Q000737:chemistry*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; D010936:Plant Extracts