A urinary metabolite of Δ1-tetrahydrocannabinol. The first synthesis of 4″,5″-bisnor-Δ1-tetrahydrocannabinol-7,3″-dioic acid, and a deuterium labelled analogue

✍ Scribed by Maria Szirmai; Magnus M. Halldin

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 807 KB
• Volume: 3
• Category: Article
• ISSN: 0968-0896
• DOI: 10.1016/0968-0896(95)00082-r

✦ Synopsis

The f'LrSt synthesis of unlabelled and [2Hs]-labelled 4",5"-bisnor-ALTHC-7,3"-dioic acid, the major dicarboxylated urinary metabolite of At-THC in man, is presented (preliminary results of this work have been presented in part at the Melbourne Symposium on Cannabis, Australia, September 1987, Ref. 1). The synthesis of methyl 3-(3,5-dihydroxyphenyl)-[3,3-2H2]propanoate ( 8) is described in a nine step sequence from 3,5-dimethoxybenzoic acid in an overall yield of 24%. Compound 8 is condensed with a terpene synthon 9 under acidic conditions, acetylated and hydrolyzed with red HgO and HgCI 2 to afford the lformyl-4",5",7-trisnor-ALTHC-3"-oic acid derivative (11). Compound 11 is oxidized using NaCIO 2 in 2-methyl-2-butene and hydrolyzed to give (+)-4",5"-bisnor-AI-THC-7,3"-dioic acid (12). The same approach has been used to prepare both the labelled and unlabelled metabolite.