Identification of Hydroxylated Cannabinoids by PMR and Mass Spectroscopy

Abstract

The stereospecific synthesis of (-)-^Δ1–3,4-trans-tetrahydrocan-nabinol (Δ¹-THC = Δ⁹-THC, IUP AC nomenclature) by Mechou-lam and Gaoni [8] and by Petrzilka et al. [11,12] has initiated a number of studies concerning the metabolic fate of Δ¹-THC and other cannabinoids in different organisms. The first major metabolite of Δ¹-THC was isolated independently by Nilsson et al. [9] and by Wall et al. [15] in 1970, and its structure was shown to be 7-OH-Δ¹THC (for the numbering of the cannabinoid skeleton, see Figure 13.1). In the meantime, the number of known metabolites has increased considerably. These include 6α,7-diOH-Δ¹-THC, 6α-OH-Δ¹THC, 6β-OH-Δ¹-THC, 1,2α-epoxy-Δ¹THC, and 6-oxo-Δ¹-THC. In addition to these metabolites, which are derived from Δ¹-THC by the introduction of an oxygen function around (or on) the isolated double bond of the isoprene moiety, another recently isolated group of metabolites contains hydroxyl groups in the aliphatic pentyl side chain of the molecule. Hydroxylation of the pentyl side chain seems to occur rather unspecificly, and compounds like 1″-OH-Δ⁶-THC, 3″-OH-Δ⁶-THC [7], 3″-OH-Δ¹-THC, and 4″-OH-Δ¹THC have been isolated [17].