Biosynthesis of the bisbenzylisoquinoline alkaloid cocsulin

Abstract

The incorporation of (±)-coclaurine, (±)-norcoclaurine, (±)-N-methylcoclaurine, and didehydro-N-methylcoclaurinium iodide into cocsulin in Cocculus laurifolius DC has been studied, and specific utilization of the (±)-N-methylcoclaurine demonstrated. The evidence supports the occurrence of oxidative dimerization of two N-methylcoclaurine units to give cocsulin. Double labelling experiments with (±)-N-methyl[1-3H, methoxy-14C]coclaurine showed that the O-methyl function from one of the N-methylcoclaurine units is lost in the bioconversion into cocsulin. Experiments with (±)-N-[14C]methyl[1-3H]coclaurine demonstrated that the hydrogen atom at the asymmetric centre in the 1-benzylisoquinoline precursor is retained in the bioconversion into cocsulin. Parallel feedings of (+)-(S)- and (–)-(R)-N-methylcoclaurines showed that the stereospecificity is maintained in the biosynthesis of cocsulin from the 1-benzylisoquinoline precursor.