Über Inhaltsstoffe des Haschisch. 2., vorläufige Mitteilung. Synthese von (−)‐Δ^{6, 1}‐3, 4‐trans‐Tetrahydrocannabinol, sowie von (±)‐Δ^{6, 1}‐3, 4‐trans‐Tetrahydrocannabinol

Abstract

Acids, such as p‐toluenesulfonic acid, mediate the direct formation of optically active (−)‐Δ6,1‐3,4‐trans‐tetrahydrocannabinol from (+)‐cis‐or (+)‐trans‐p‐menthadiene‐(2,8)‐ol‐(1) and olivetol.

Cannabidiol Discovery and Synthesis—a Target‐Oriented Analysis in Drug Production Processes

“…On the other hand, stronga cids (e.g.,m ethanesulfonic acid, trifluoroacetic acid, or p-TsOH) under reflux provide D 8À -THC (8)a samain product. [144][145][146] The formation of 8 could be via CBD as an intermediate, since (À)-2 can undergo intramolecular cyclization in the presence of p-TsOH. 121 Moreover,R azdane tal.…”

“… [121, 143] For example, condensation of 26 with 27 in the presence of weak acids (e.g., oxalic acid, maleic acid, or p ‐toluenesulfonic acid ( p ‐TsOH)) and at temperatures around 20 °C or lower result in (−)‐ 2 , also forming byproducts 40 and 41 in a similar distribution to that of DMF‐derived acetal‐mediated 39 reactions (Figure 4). On the other hand, strong acids (e.g., methanesulfonic acid, trifluoroacetic acid, or p ‐TsOH) under reflux provide Δ 8− ‐THC ( 8 ) as a main product [144–146] . The formation of 8 could be via CBD as an intermediate, since (−)‐ 2 can undergo intramolecular cyclization in the presence of p ‐TsOH.…”

Synthetic pathways to tetrahydrocannabinol (THC): an overview

“…Shortly after the publication of Mechoulam, the use of enantiopure chiral pool terpenoids became common practice in cannabinoid synthesis. Elaborating on an earlier procedure, 22 Petrzilka and co-workers reported a stereoselective synthesis of (−)-trans-Δ 8 -THC (9) starting from p-mentha-2,8-dien-1-ol (18). 23 Using this terpenoid, olivetol (11) and p-TSA, electrophilic aromatic substitution provided (−)-trans-CBD (5), which upon renewed exposure to p-TSA cyclised to (−)-trans-Δ 9 -THC (7, not shown), followed by in situ isomerisation to the thermodynamically more stable (−)-trans-Δ 8 -THC (9) in 53% yield (Scheme 4A).…”

“Herbal incense”: Designer drug blends as cannabimimetics and their assessment by drug discrimination and other in vivo bioassays

“…Once the exact structure of THC had been elucidated, routes for its synthesis were explored in order to improve chemical efficiency and yield (Mechoulam and Gaoni, 1967; Petrzilka, 1971; Petrzilka and Sikemeier, 1967; Razdan, 1986). These efforts set the stage for the initial scientific efforts to better understand the pharmacology of cannabis, including pharmacokinetics and bio-distribution (Agurell et al, 1986; Pertwee, 2006).…”