1969/01/01 by T. Petrzilka, Th. Petrzilka, W. Haefliger +1 · 5 citations
Medicine · Chemistry · Agricultural and Biological Sciences · #Cannabis and Cannabinoid Research #Carbohydrate Chemistry and Synthesis #Natural Compound Pharmacology Studies
paper · doi:10.1002/hlca.19690520427
Abstract (−)‐Cannabidiol has been synthesized from (+)‐ cis ‐ and (+)‐ trans ‐ p ‐menthadien‐(2, 8)‐ol‐(1) and olivetol, using N, N‐dimethylformamide dineopentyl acetal or weak acids, such as oxalic, picric, or maleic acid, as catalysts. Since the chirality of (+)‐ trans ‐ p ‐menthadien‐(2, 8)‐ol‐(1) is known, the above synthesis constitutes an unambiguous prove for the absolute configuration of (−)‐cannabidiol and the two isomeric (−)‐6a, 10a‐ trans ‐tetrahydrocannabinols. If stronger acids, such as p ‐toluenesulfonic, trifluoroacetic, or hydrochloric acid, are used as mediators for the reaction, (−)‐Δ 8 ‐6a, 10a‐ trans ‐tetrahydrocannabinol is obtained as the main product. Transformation of the thermodynamically more stable Δ 8 ‐tetrahydrocannabinol into the less stable Δ 9 ‐isomer was achieved in a practically quantitative yield by addition of hydrochloric acid and elimination of the elements of hydrochloric acid by means of potassium t ‐amylate. If resorcinols I were used instead of olivetol in the condensation reaction with strong acids, the corresponding homologues of Δ 8 ‐tetrahydrocannabinol were obtained in varying yields.