Asymmetric total synthesis of tetrahydroprotoberberine derivatives and evaluation of their binding affinities at dopamine receptors

Bioorg Med Chem Lett. 2017 Mar 15;27(6):1437-1440. doi: 10.1016/j.bmcl.2017.01.090. Epub 2017 Jan 31.

Abstract

Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. l-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites l-ICP, l-CD, and l-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors. The synthesis of these bioactive metabolites will allow further in vivo study of their potential in treating cocaine addiction.

Keywords: Cocaine; Dopamine receptor; Tetrahydroprotoberberine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Berberine Alkaloids / chemical synthesis*
  • Berberine Alkaloids / metabolism
  • Binding Sites
  • Humans
  • Radioligand Assay
  • Receptors, Dopamine / metabolism*

Substances

  • Berberine Alkaloids
  • Receptors, Dopamine
  • berbine