Scalable Total Synthesis, IP3R Inhibitory Activity of Desmethylxestospongin B, and Effect on Mitochondrial Function and Cancer Cell Survival

Angew Chem Int Ed Engl. 2021 May 10;60(20):11278-11282. doi: 10.1002/anie.202102259. Epub 2021 Apr 8.

Abstract

The scalable synthesis of the oxaquinolizidine marine natural product desmethylxestospongin B is based on the early application of Ireland-Claisen rearrangement, macrolactamization, and a late-stage installation of the oxaquinolizidine units by lactam reduction. The synthesis serves as the source of material to investigate calcium signaling and its effect on mitochondrial metabolism in various cell types, including cancer cells.

Keywords: IP3R receptor; cancer; metabolism; total synthesis; xestospongins.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / antagonists & inhibitors*
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Molecular Structure

Substances

  • Antineoplastic Agents
  • Biological Products
  • Inositol 1,4,5-Trisphosphate Receptors