Synthesis and biological evaluation of (-)-6-O-desmethylcryptopleurine and analogs

Bioorg Med Chem Lett. 2015 Jan 15;25(2):184-7. doi: 10.1016/j.bmcl.2014.11.086. Epub 2014 Dec 6.

Abstract

(-)-Cryptopleurine 1 is one of the most potent anti-proliferative member of the phenanthroquinolizidine class of alkaloids. We report here the synthesis of (-)-6-O-desmethylcryptopleurine (-)-2 and (-)-6-O-desmethyl-(15R)-hydroxycryptopleurine (-)-4 in their enantiomerically enriched form through a convergent synthetic route, where the chirality is introduced by the use of commercially available (R)-methyl piperidine-2-carboxylate hydrochloride 17. Anti-proliferative activities of these compounds were evaluated on a panel of four cancer cell lines, revealing that compounds (-)-2 and (-)-4 are potent cytotoxic compared to cryptopleurine.

Keywords: (−)-Cryptopleurine; Cytotoxicity; Phenanthroquinolizidine alkaloid.

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Drug Evaluation, Preclinical / methods
  • Humans

Substances

  • Alkaloids
  • cryptopleurine