Karamomycins A-C: 2-Naphthalen-2-yl-thiazoles from Nonomuraea endophytica

J Nat Prod. 2019 Apr 26;82(4):870-877. doi: 10.1021/acs.jnatprod.8b00928. Epub 2019 Mar 25.

Abstract

Karamomycins A-C (2-4), the first natural 2-naphthalen-2-yl-thiazole derivatives, were isolated along with a plausible precursor molecule, 1-hydroxy-4-methoxy-2-naphthoic acid (1), uracil, 1-acetyl-β-carboline, and actinomycin C2 from the culture broth of the terrestrial actinomycete strain GW58/450, identified as Nonomuraea endophytica. These compounds were characterized by analysis of their NMR and mass spectrometry (MS) data; the absolute configurations of 2 and 4 were determined by comparison of 13C NMR, NOESY, and circular dichroism (CD) spectra with density functional theory (DFT)-calculated data. In karamomycin C (4), the thiazole of 2 is connected to an unusual iminothiazolo[4,3- c][1,4]thiazepinone, for which we proposed a biosynthetic origin from two cysteine residues. It is closely related to ulbactin F; however, the heterocycle is enantiomeric to the latter and connected to phenol instead of 4-methoxy-1-naphthol. Karamomycins A (2) and C (4) were cytotoxic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / chemistry*
  • Anti-Infective Agents / pharmacology
  • Biological Products / chemistry
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology
  • Cell Line, Tumor
  • Circular Dichroism
  • Density Functional Theory
  • Drug Screening Assays, Antitumor
  • Humans
  • Mass Spectrometry
  • Molecular Structure
  • Naphthalenes / chemistry
  • Naphthalenes / isolation & purification*
  • Naphthalenes / pharmacology
  • Nuclear Magnetic Resonance, Biomolecular
  • Thiazoles / chemistry
  • Thiazoles / isolation & purification*
  • Thiazoles / pharmacology

Substances

  • Anti-Infective Agents
  • Biological Products
  • Naphthalenes
  • Thiazoles

Supplementary concepts

  • Nonomuraea endophytica