A urinary metabolite of delta 1-tetrahydrocannabinol. The first synthesis of 4",5"-bisnor-delta 1-tetrahydrocannabinol-7,3"-dioic acid, and a deuterium labelled analogue.
The first synthesis of unlabelled and [2H5]-labelled 4",5"-bisnor-delta 1-THC-7,3"-dioic acid, the major dicarboxylated urinary metabolite of delta 1-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 HgCl2 to afford the 1-formyl-4",5",7-trisnor-delta 1-THC-3"-oic acid derivative (11). Compound 11 is oxidized using NaClO2 in 2-methyl-2-butene and hydrolyzed to give (+/-)-4",5"-bisnor-delta 1-THC-7,3"-dioic acid (12). The same approach has been used to prepare both the labelled and unlabelled metabolite.
Szirmai
M
M
Department of Pharmacognosy, Uppsala University, Sweden.
Halldin
M M
MM
D003903:Deuterium; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000652:urine; D006801:Humans; D007553:Isotope Labeling; D015394:Molecular Structure
C065093:4'',5''-bisnor-delta(1)-tetrahydrocannabinol-7,3''-dicarboxylic acid; D013759:Dronabinol; D003903:Deuterium