Biosynthesis of cannabinoids -: Incorporation experiments with 13C-labeled glucoses

The biosynthesis of cannabinoids was studied in cut sprouts of Cannabis sativa by incorporation experiments using mixtures of unlabeled glucose and [1-C-13]glucose or [U-C-13(6)]glucose. C-13-labeling patterns of cannabichromenic acid and tetrahydrocannabinolic acid were analyzed by quantitative NMR spectroscopy. C-13 enrichments and coupling patterns show that the C-10-terpenoid moiety is biosynthesized entirely or predominantly (> 98%) via the recently discovered deoxyxylulose phosphate pathway. The phenolic moiety is generated by a polyketide-type reaction sequence. The data support geranyl diphosphate and the polyketide, olivetolic acid, as specific intermediates in the biosynthesis of cannabinoids.