Short Route to the Total Synthesis of Natural Muricadienin and Investigation of Its Cytotoxic Properties

  • J Nat Prod. 2016 Aug 26;79(8):2039-44. doi: 10.1021/acs.jnatprod.6b00335.
Usein M Dzhemilev  1 ,  Vladimir A D'yakonov  1 ,  Regina A Tuktarova  1 ,  Lilya U Dzhemileva  1  2  3 ,  Svetlana R Ishmukhametova  1 ,  Milyausha M Yunusbaeva  3 ,  Armin de Meijere  4
Affiliations
  • 1. Laboratory of Catalytic Synthesis, Institute of Petrochemistry and Catalysis of RAS (IPC RAS) , Prospect Octyabrya, 141, 450075, Ufa, Russian Federation.
  • 2. Department of Immunology and Human Reproductive Health, Bashkir State Medical University , Lenin Street, 3, 450003, Ufa, Russian Federation.
  • 3. Institute of Biochemistry and Genetics, Ufa Scientific Centre of Russian Academy of Sciences , Prospect Octyabrya, 71, 450054, Ufa, Russian Federation.
  • 4. Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen , Tammannstrasse 2, 37077 Göttingen, Germany.
PMID: 27533261 DOI: 10.1021/acs.jnatprod.6b00335
Abstract

An original synthesis of the acetogenin muricadienin, the bioprecursor of solamin, has been developed. The key step in the five-step 41% overall yield synthesis is the catalytic cross-cyclomagnesiation reaction of functionally substituted 1,2-dienes with EtMgBr in the presence of Cp2TiCl2 and magnesium metal. It has been demonstrated for the first time that muricadienin exhibits a moderate in vitro inhibitory activity against topoisomerases I and IIα, key cell cycle Enzymes. Using flow cytometry, muricadienin was shown to have high cytotoxicity toward the HEK293 kidney Cancer cells (IC50 0.39 μM).