Synthesis of isoquinoline alkaloids from barakol

Abstract

Barakol, cassiarins A and B are biological active compounds extracted from leaves of Cassia siamea. Barakol, with an unprecedented tricyclic core structure similar to cassiarins A and B, is a major constituent in leaves of Cassia siamea. Cassiarins A and B, which have been known to exhibit potent antiplasmodial activity against Plasmodium falciparum, could be extract from the natural source in low yield. Therefore, transformation of barakol to its bioactive isoquinoline alkaloids as cassiarins A and B has been investigated. Synthesis of cassiarin A started from a conversion of barakol to its more stable anhydrobarakol chloride, followed by a reaction with ammonium hydroxide and subsequently reacted with acid to form the cassiarin A. Similarly, cassiarin B and its derivative bearing different N-substituents was synthesized by the reaction of anhydrobarakol chloride and methyl-4-aminobutyrate or the other primary amine, such as butylamine, cyclohexylamine, aniline and benzylamine. All new cassiarin derivatives exhibited negative antiplasmodial activity against Plasmodium falciparum and cytotoxic activity against cancer cell.