[Alkaloids with cardiovascular activities--synthesis of protoberberine]

It has been reported that berberine (BR) has positive inotropic and negative chronotropic effects. Recently, it has been tried in patients with arrhythmia and congestive heart failure. But BR, a quaternary ammonium salt, is absorbed poorly. We took BR as leading compound to synthesize its derivatives in order to find orally active agents. Compounds substituted by -OCH3 in different positions of the D ring were synthesized. In the screening of inhibition of electrically induced contraction of isolated guinea pig left atria and spontaneous beating of its right atria, the synthesized compounds were found to possess activity of inhibiting spontaneous beating of isolated guinea pig right atria. Compound I4 was shown to be the most effective of the synthesized compounds with IC50 value of 4.34 (mumol). The IC50 value of BR was 204 (mumol).