SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF YDROXY-3-(1',1'-DIMETHYLHEPTYL)HEXAHYDROCANNABINOL - A HIGH-AFFINITY CANNABINOID AGONIST

ydroxy-3-(1',1'-dimethylheptyl)hexahydrocannabinol (1) was synthesized from the known cannabimimetic analog (+/-)-nabilone. Racemic 1 was re solved by HPLC on a semipreparative CHIRALCEL OD column (Daicel, Inc.) , and pharmacological activities of the individual enantiomers were ev aluated in the mouse model. The (-)-enantiomer was found to be much mo re potent than the (+)-enantiomer in all the four measures with the po tency ratios in the production of catalepsy (RI), hypoactivity (SA), h ypothermia (RT), and antinociception (TF) being 93, 143, 186, and 322, respectively. The racemic 11 alpha-OH diastereomer (2), a reaction si de product, was also evaluated in the mouse model. Only small differen ces in the pharmacological activity of racemic 1 and 2 were found in t he above four measures.