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

Abstract

SUMMARYThe first synthesis of 4"-hydroxy-A1-THC-7-oic acid, one of the three major metabolites of AI-THC identified in human urine is discussed. Methyl 4-(3,5-dihydroxyphenyl)butanoate (8) was prepared from 3,5-dihydmxybenzoic 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 NaBQ afforded the secondary alcohol in the side-chain. Acetylation and removal of the 13-dithiane masking group gave the aldehyde in C-7-position which was further oxidized using N a C Q followed by deacetylation to give the desired metabolite 14. The same procedure may be used for the synthesis of unlabelled 4"-hydroxy-A*-THC-7-oic acid.