Biosynthesis of isotetrandrine

The incorporation of (±)-coclaurine, (±)-N-methylcoclaurine, didehydro-N-methylcoclaurinium iodide, (+)-(S)-N-methylcoclaurine and (?)-(R)-N-methylcoclaurine into isotetrandrine in Cocculus laurifolius DC has been studied and specific utilization of (±)-, (+)-(S)- and (?)-R-N-methylcoclaurines and didehydro-N-methylcoclaurinium iodide demonstrated. The evidence supports intermolecular oxidative coupline of (+)-(S)- and (?)-(R)-N-methylcoclaurines to form isotetrandrine. Double labelling experiment with (±)-N- ¹⁴C] methyl 1 - ³H] coclaurine demonstrated that the hydrogen atom at the asymmetric centre in N-methylcoclaurine is retained in the bioconversion into isotetrandrine.