Elucidation of the Relationship between CD Cotton Effects and the Absolute Configuration of Sixteen Stereoisomers of Spiroheterocyclic-Lactams

Mar Drugs. 2018 Jun 29;16(7):223. doi: 10.3390/md16070223.

Abstract

As part of research to search for antitumor agents in fungi originating from marine organisms, cephalimysins E⁻L were isolated from a culture broth of Aspergillus fumigatus that was separated from the marine fish Mugil cephalus. One- and two-dimensional nuclear magnetic resonance spectra revealed their planar structures, which are diastereomers of each other. Their absolute stereostructures were established by epimerization at C-8 with acidic methanol, nuclear Overhauser effect spectroscopy (NOESY), and circular dichroism (CD) spectroscopy. These demonstrated the detailed relationships between absolute configuration and CD Cotton effects. Additionally, in the growth inhibition assay against P388, HL-60, L1210, and KB cell lines, some of the fungal metabolites or reaction products exhibited moderate activities.

Keywords: Aspergillus fumigatus; Mugil cephalus; cephalimysins; circular dichroism spectroscopy; cytotoxicity; marine microorganism; spiro-heterocyclic γ-lactam.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Aquatic Organisms / chemistry
  • Aspergillus fumigatus / chemistry
  • Cell Line, Tumor
  • Circular Dichroism / methods
  • Fishes / metabolism
  • HL-60 Cells
  • Humans
  • KB Cells
  • Lactams / chemistry*
  • Magnetic Resonance Spectroscopy / methods
  • Molecular Structure
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Lactams