Total syntheses and cytotoxicity of kealiiquinone, 2-deoxy-2-aminokealiiquinone and analogs

Bioorg Med Chem Lett. 2013 Nov 15;23(22):6183-7. doi: 10.1016/j.bmcl.2013.08.093. Epub 2013 Sep 6.

Abstract

Concise syntheses of two Leucetta-derived naphthimidazole alkaloids, kealiiquinone and 2-deoxy-2-aminokealiiquinone, are described based on a biosynthetic-guided hypothesis. Advanced intermediates containing the full naphthimidazole framework are constructed through Friedel-Crafts chemistry followed by oxidation of the electron rich C-ring with hydrogen peroxide. The cytotoxicity of these alkaloids in a breast cancer cell line along with several closely related marine-derived natural products kealiinines A-C and analogs are reported.

Keywords: Biomimetic; Cytotoxicity; Leucetta alkaloids; Naphthimidazole; Oxidation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Animals
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Molecular Structure
  • Naphthoquinones / chemical synthesis*
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology*
  • Oxidation-Reduction
  • Porifera / chemistry
  • Stereoisomerism

Substances

  • Alkaloids
  • Imidazoles
  • Naphthoquinones