Biosynthesis of isotetrandrine

Abstract 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- [ 14 C] methyl [1 - 3 H] coclaurine demonstrated that the hydrogen atom at the asymmetric centre in N-methylcoclaurine is retained in the bioconversion into isotetrandrine.