Protecting-Group-Free Total Synthesis and Biological Evaluation of 3-Methylkealiiquinone and Structural Analogues

J Org Chem. 2018 Sep 7;83(17):10627-10635. doi: 10.1021/acs.joc.8b01436. Epub 2018 Aug 22.

Abstract

The modular protecting-group-free total synthesis of 3-methylkealiiquinone, an analogue of the marine alkaloid kealiiquinone, was accomplished in seven steps. A regioselectively constructed functionalized arylbenzimidazolone moiety and dimethyl squarate were used as the only two building blocks. A thermal ring expansion via 6π-conrotatory ring closure to build the quinone fragment gave rise to the desired linear analogue of the natural compound along with a nondescribed structurally attractive angular naphtho[1,2- d]imidazole regioisomer. The IC50 values for the compounds were determined on three cancer cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic
  • Humans
  • Imidazoles / chemistry
  • Inhibitory Concentration 50
  • Quinones / chemical synthesis*
  • Quinones / chemistry
  • Quinones / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Quinones