Preparative Scale MS-Guided Isolation of Bioactive Compounds Using High-Resolution Flash Chromatography: Antifungals from Chiloscyphus polyanthos as a Case Study

Planta Med. 2016 Jul;82(11-12):1051-7. doi: 10.1055/s-0042-108207. Epub 2016 Jun 23.

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.

MeSH terms

  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology
  • Biological Products / chemistry*
  • Candida albicans / drug effects
  • Chromatography, High Pressure Liquid / methods*
  • Hepatophyta / chemistry*
  • Molecular Structure
  • Plant Extracts / chemistry*
  • Tandem Mass Spectrometry / methods*

Substances

  • Antifungal Agents
  • Biological Products
  • Plant Extracts