Copper(I) mediated facile synthesis of potent tubulin polymerization inhibitor, 9-amino-α-noscapine from natural α-noscapine

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2983-7. doi: 10.1016/j.bmcl.2012.02.033. Epub 2012 Feb 21.

Abstract

Facile synthesis of natural α-noscapine analogue, 9-amino-α-noscapine, a potent inhibitor of tubulin polymerization for cancer therapy, is achieved via copper(I) iodide mediated in situ aromatic azidation and reduction of 9-bromo-α-noscapine (obtained by bromination of natural α-noscapine) with NaN(3) in DMSO at 130°C in the presence of L-proline as an amino acid promoter. The protocol developed here avoided isolation of 9-azido-α-noscapine and did not cleave the sensitive C-C bond between two heterocyclic phthalide and isoquinoline units.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Copper / chemistry*
  • Models, Molecular
  • Noscapine / analogs & derivatives*
  • Noscapine / chemical synthesis
  • Noscapine / chemistry
  • Noscapine / pharmacology
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry

Substances

  • 9-amino-alpha-noscapine
  • Tubulin Modulators
  • Copper
  • Noscapine