A urinary metabolite of Δ1-tetrahydrocannabinol. The first synthesis of 4''-hydroxy-Δ1-tetrahydrocannabinol-7-oic acid labelled with deuterium

Article abstract of DOI:10.1002/(SICI)1099-1344(199604)38:4<309::AID-JLCR775>3.0.CO;2-5

The first synthesis of 4''-hydroxy-Δ¹-THC-7-oic acid, one of the three major metabolites of Δ¹-THC identified in human urine is discussed. Methyl 4-(3,5-dihydroxyphenyl)butanoate (8) was prepared from 3,5-dihydroxybenzoic acid in an overall yield of 15%. 8 was condensed with a terpene synthon (9) under acidic conditions followed by hydrolysis and conversion of the 4''-carboxylic acid function to the corresponding methyl ketone using methyllithium. Reduction with NaBH₄ afforded the secondary alcohol in the side-chain. Acetylation and removal of the 1,3-dithiane masking group gave the aldehyde in C-7-position which was further oxidized using NaClO₂ followed by deacetylation to give the desired metabolite 14. The same procedure may be used for the synthesis of unlabelled 4''-hydroxy-Δ¹-THC-7-oic acid.