Absolute configuration and biosynthesis of (+)-sinactine

Abstract

The incorporation of norreticuline, reticuline and nororientaline into sinactine in Cocculus laurifolius DC has been studied and specific utilization of reticuline demonstrated. Feeding with N-[¹⁴CH₃]reticuline showed that the C atom 8 in sinactine is derived from N-Me group of reticuline. Feeding of (±)-[1-³H, 3-¹⁴C]norreticuline and degradation of biosynthetic sinactine established that the regiospecificity is maintained in the bioconversion of 1-benzyltetrahydroisoquinoline precursor into the tetrahydroprotoberberine alkaloid. Further feeding of doubly labelled precursor demonstrated that the H atom at the asymmetric centre in reticuline is retained in the bioconversion into sinactine. Feedings of labelled scoulerine and tetrahydropalmatrubine established the intermediacy of scoulerine in the biosynthesis and suggested that the methylenedioxy group formation probably precedes O-methylation in the bioconversion of scoulerine into sinactine. Parallel feedings of (R)-, and (S)-reticulines and chemical conversion of (+)-sinactine into (+)-(R)-tetrahydropalmatine established that (+)-sinactine has R-configuration at the asymmetric centre C-13a.