Synthesis of [2H6]-labelled metabolites of cannabinoids

Article abstract of DOI:10.1002/1099-1344(200006)43:7<655::AID-JLCR350>3.0.CO;2-T

Four [²H₆]-labelled metabolites of cannabinoids were synthesized for use as internal standards for GC/MS analysis. The hexadeutero-ketone 3, prepared from ketal 1, undergoes a Shapiro reaction to give (±)-6,6-[²H₆]dimethyl-11-nor-9-carboxy-Δ⁹-THC (4a) as the major product. The minor product, (±)-6,6-[²H₆]dimethyl-11-nor-9-carboxy-Δ⁸-THC (4b), was obtained after hydrolysis of its acetate methyl ester which was isolated using preparative HPLC. Reduction of 4a gave (±)-6,6-[²H₆]dimethyl-11-hydroxy-Δ⁹-THC (6). (±)-6,6-[²H₆]dimethyl-8β,11-dihydroxy-Δ⁹-THC (10), was also prepared from 3 using a reported procedure for the non-labelled analog.