The Rickiols: 20-, 22-, and 24-membered Macrolides from the Ascomycete Hypoxylon rickii

Chemistry. 2018 Feb 9;24(9):2200-2213. doi: 10.1002/chem.201704928. Epub 2018 Jan 19.

Abstract

In preceding studies the neotropical ascomycete Hypoxylon rickii turned out to be a prolific source of new secondary metabolites, considering that we had obtained terpenoids with five different scaffolds along with a series of terphenyls. From the mycelial extracts of a 70 L scale fermentation of this strain we additionally isolated nine new macrolides (1-9) by RP-HPLC. The planar structures were elucidated by NMR spectroscopy complemented by HR-ESIMS. The relative configurations were assigned by J-based configuration analyses and confirmed by Kishi's Universal Database. Subsequently, the absolute configurations were assigned by Mosher's method using the shift analysis of a tetra-MTPA derivative. For rickiol A (1) and E (5) we observed transesterification of 20-membered ring structures to 22-membered isomers rickiol A2 (6) and E2 (7), and to 24-membered isomers rickiol A3 (8) and rickiol E3 (9), respectively. Cytotoxic effects and moderate antibiotic activity against Gram-positive bacteria were observed for 1-8 and 1-6 and 8, respectively. The total synthesis of rickiol E3 (9) established easier access to these compounds.

Keywords: Kishis′s Universal Database; Mosher's method; macrolide; polyketides; total synthesis.

MeSH terms

  • Animals
  • Ascomycota / chemistry*
  • Ascomycota / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Chromatography, Reverse-Phase
  • Fungi / drug effects
  • Gram-Positive Bacteria / drug effects
  • HeLa Cells
  • Humans
  • Isomerism
  • Macrolides / chemical synthesis
  • Macrolides / chemistry*
  • Macrolides / isolation & purification
  • Macrolides / pharmacology
  • Magnetic Resonance Spectroscopy
  • Mice
  • Microbial Sensitivity Tests
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Macrolides