Cannabinoid metabolites, oxygenated

In a study looking at oxygenated metabolites of AEA and their interaction with the cannabinoid system, a series of hydroxylated alkyl chains was prepared using different lipoxygenases as biocatalysts [152-154]. Of the seven AEA derivatives prepared, only the 5R-hydroxy (208), 125 -hydroxy (209) and 155 -hydroxy (210) derivatives had any affinity for the CBi receptor. Interestingly, the IdV-hydroxy compound (211) that was inactive at the CBi receptor displayed some affinity for the CB2 receptor [152] (see Table 6.18). 

The metabolic functionalization of cannabinoids is of continuing interest (c/. Vol. 4, p. 71 Vol. 7, p. 50). A -THC may be hydroxylated at C-4 using Mycobacterium rhodochrous (together with aromatization) or at C-4" of the side-chain with Bacillus cereus or may be oxygenated at C-5 with Streptomyces species. A -THC has been hydroxylated in both the ring system and the side-chain with Pellicularia filamentosa and Streptomyces lavendulae, and further evidence in favour of in vivo epoxy metabolites and derivatives in the mouse has been presented (cf. Vol. 4,... 

Van der Stelt, M., Van Kuik, J.A., Bari, M., Van Zadelhoff, G., Eeeflang, B.R., Veldink, G.A., Einazzi-Agro, A., Vliegenthart, J.F.G., and Maccarrone, M. (2002). Oxygenated metabolites of anandamide and 2-arachidonoylglycerol conformational analysis and interaction with cannabinoid receptors, membrane transporter, and fatty acid amide hydrolase. J. Med. Chem., 45, 3709-3720. 

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