LC-MS- and (1)H NMR Spectroscopy-Guided Identification of Antifungal Diterpenoids from Sagittaria latifolia

J Nat Prod. 2015 Sep 25;78(9):2255-9. doi: 10.1021/acs.jnatprod.5b00470. Epub 2015 Sep 15.


Antifungal screening of small-molecule natural product libraries showed that a column fraction (CF) derived from the plant extract of Sagittaria latifolia was active against the fungal pathogen Cryptococcus neoformans. Dereplication analysis by liquid chromatography-mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy ((1)H NMR) indicated the presence of new compounds in this CF. Subsequent fractionation of the plant extract resulted in the identification of two new isopimaradiene-type diterpenoids, 1 and 2. The structures of 1 and 2 were determined by chemical methods and spectroscopic analysis as isopimara-7,15-dien-19-ol 19-O-α-l-arabinofuranoside and isopimara-7,15-dien-19-ol 19-O-α-l-(5'-acetoxy)arabinofuranoside, respectively. Compound 1 exhibited IC50 values of 3.7 and 1.8 μg/mL, respectively, against C. neoformans and C. gattii. Its aglycone, isopimara-7,15-dien-19-ol (3), resulting from acid hydrolysis of 1, was also active against the two fungal pathogens, with IC50 values of 9.2 and 6.8 μg/mL, respectively. This study demonstrates that utilization of the combined LC-MS and (1)H NMR analytical tools is an improved chemical screening approach for hit prioritization in natural product drug discovery.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology*
  • Cryptococcus / drug effects
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology*
  • Drug Discovery
  • Glycosides / chemistry
  • Glycosides / isolation & purification*
  • Glycosides / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Pyridones
  • Sagittaria / chemistry*
  • Small Molecule Libraries
  • Wisconsin


  • Antifungal Agents
  • Diterpenes
  • Glycosides
  • Pyridones
  • Small Molecule Libraries
  • isopimara-7,15-dien-19-ol 19-O-alpha-L-(5'-acetoxy)arabinofuranoside
  • isopimara-7,15-dien-19-ol 19-O-alpha-L-arabinofuranoside
  • tolypyridone A