Salvinorin A, a potent kappa-opioid receptor agonist from the hallucinogenic plant Salvia divinorum, is biosynthesized via the 1-deoxy-D-xylulose-5-phosphate (DXP) pathway, not the classic mevalonic acid pathway. This was determined by feeding microshoots with isotopically labeled precursors and analyzing the resulting salvinorin A (2.7 mg from 200 microshoots) using NMR and HR-ESI-MS. Incorporation of labeled glucose and 1-deoxy-D-xylulose confirmed the DXP pathway, while labeled methionine showed that methylation of the C-4 carboxyl group is catalyzed by a type III S-adenosyl-L-methionine-dependent O-methyltransferase.
The hallucinogenic neoclerodane diterpenoid salvinorin A has its complete hydrogen and carbon nuclear magnetic resonance (NMR) spectral assignments determined in three different NMR solvents using HSQC, HMBC, and COSY techniques. Solvent systems that resolve all hydrogen signals are described. Virtual coupling is observed for protons at positions C-2, C-3, and C-4 in the 600 MHz hydrogen spectrum in CDCl3. Complete assignments for the hydrogen and carbon NMR spectra of salvinorin B are also reported.