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

作者：Lee David Y W^*; Liu Jing; Zhang Shuzhen; Huang Peng; Liu Chen Lee Yuan

来源：Bioorganic & Medicinal Chemistry Letters, 2017, 27(6): 1437-1440.

DOI：10.1016/j.bmcl.2017.01.090

• Tetrahydroprotoberberine
• Cocaine
• Dopamine receptor

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.

• 出版日期2017-3-15