Biosynthesis of cocsulinin

Abstract

The incorporation of (±)-norcoclaurine, (±)-coclaurine, and (±)-N-methylcoclaurine into cocsulinin in Cocculus laurifolius DC has been studied, and specific utilization of the (±)-N-methylcoclaurine has been demonstrated. The evidence supports oxidative dimerisation of two N-methylcoclaurine units to give cocsulinin. Experiments with (±)-N-[¹⁴C]methyl[1-³H]coclaurine have demonstrated that the hydrogen atom at the asymmetric centre in the 1-benzylisoquinoline precursor is retained in the bioconversion into cocsulinin. Parallel feedings of (+)-(S)- and (–)-(R)-N-methylcoclaurines showed that the configuration at C-1 is maintained in the biosynthesis of cocsulinin from the 1-benzylisoquinoline precursor.

A double-labelling experiment with (±)-N-methyl[1-³H, 6-O-methyl-¹⁴C]coclaurine has shown that the 6-O-methyl group of an N-methylcoclaurine unit is lost in the biotransformation into cocsulinin. Incorporation of (+)-(S,S)-O-methylcocsulinin established that de-O-methylation is the terminal step in the biosynthesis of cocsulinin.