Tetrahydrocannabinol structure

Roger Adams (1889-1971) wa s born in Boston, Massachusetts, and received his Ph.D. in 1912 at Harvard. He taught at the University of Illinois from 1916 until his retirement in 1957, during which lime he had an enormous influence on the development of organic chemistry in the United States. Among many other accomplishments, he established the structure of tetrahydrocannabinol, the active ingredient in marijuana. 

Endocannabinoids. Figure 1 Chemical structures of the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol, of Cannabis sativa psychoactive principle, A9-tetrahydrocannabinol, and of the CB-i receptor antagonist/inverse agonist, rimonabant. 

This compound and its related acidic form, A8-tetrahydrocannabinolic acid (A8-THCA, 2.13) are structural isomers of A9-THC. Although it is the thermodynamically stable form of THC, A8-THC (2.14) contributes approximately only 1% to the total content of THC in C. sativa. In the synthetic production process, A8-THC is formed in significantly higher quantities than in plants. 

A serious problem in the early Western medicinal use of C. sativa, mainly as a tincture, was its highly variable activity and inconsistent results. Medicinal preparations have to handle several particularities due to the structure of the active ingredients of C. sativa. The identity of the main active constituent of C. sativa, A9-tetrahydrocannabinol (INN dronabinol) remained unknown until 1964 [128] standardized C. sativa preparations were not available. The plant itself is found in several different chemotypes, which added to the unpredictable nature of early medicinal preparations. 

Oh, nonsense," I said and got up and went to the blackboard and drew the structure of the target. I drew the isomeric homologue of tetrahydrocannabinol with the terpene double bond down in the terpene 3,4-position and a 1,2-dimethylheptyl chain at the aromatic 3-position. "This is the obvious product you want," 1 added as 1 returned to my seat, "So why don t we discuss how this coupling could be achieved."... 

The advances in isolation methods made possible a clarification of the chemistry of cannabis. In 1963, our group reisolated CBD and reported its correct structure and stereochemistry. A year later we finally succeeded in isolating pure A -tetrahydrocannabinol (A -THC), elucidated its structure, obtained a crystalline derivative and achieved a partial synthesis from CBD. Several years later, a minor psychotomimetically active constituent, A -THC, was isolated from marijuana. Whether this THC isomer is a natural compound, or an artifact formed during the drying of the plant, remains an open problem. 

Adams R, Loewe S, Pease DC, Cain CK, Wearn RB, Baker BR, Wolff H, Structure of cannabidiol. VIII. Position of the double bonds in cannabidiol. Marihuana activity of tetrahydrocannabinols, J Amer Chem Soc 62 2566—2567, 1940. 

Adams R, Baker BR, Structure of Cannabidiol. VII. A Method of Synthesis of a Tetrahydrocannabinol which Possesses Marihuana Activity, J Amer Chem Soc 62 2405-2408, 1940. 

Adams R,Pease DC, Cain CK, Clark JH, Structure of cannabinol. VI. Isomerization of cannabidiol to tetrahydrocannabinol, a physiologically active product. Conversion of cannabidiol to cannabinol, J Amer Chem Soc 62 2402—2405, 1940. 

Cannabis sativa plants contain at least 400 different compounds, of which as many as 60 are structurally related to 5 -tetrahydrocannabinol (5 -THC), the primary psychoactive constituent of cannabis. When cannabis is smoked, hundreds of additional compounds are produced by pyrolysis, which may contribute to both acute and chronic effects (Abood and Martin, 1992). The central nervous system actions of canna-binoids are mediated primarily through the CBj receptor. A second type of cannabinoid receptor, termed the CB2 receptor, is distributed primarily in the periphery (Gifford et ah, 1999). Activation of central cannabinoid receptors modulates neurotransmitter release at... 

Figure 30-29 Structures of the active components of cannabis, tetrahydrocannabinol, and cannabidiol, and structures of endogenous cannabinoids and of the vanilloid lipid capsaicin.

Evans, and later j0rgensen, studied the counterion effect of these Cj-symmetric bis(oxa-zoline)/Cu(II) complexes, and found that the counterion structure dramatically affected the catalytic efficiency, and SbFg- was the best among the anions examined (SbF6>PF6>OTf>BF4) [27,28] (Eq. 8A.15). This cationic bis(oxazoline)/Cu(II) catalyst has been successfully applied to asymmetric synthesis of enr-A1 -tetrahydrocannabinol [29] and enf-shikimic acid [30]. 

FIGURE 18.2 Chemical structures of A9-tetrahydrocannabinol (A9-THC) derived from marijuana, and the endogenous cannabimimetic eicosanoid, anadamide (arachidonylethanolamide), identified in the human brain. 

The psychoactive and medicinal chemical compounds found in the resin of the marijuana plant are known as cannabinoids. The cannabis plant contains more than 460 known compounds over 60 of these have a cannabinoid structure. The only cannabinoid that is highly psychoactive and present in large amounts in the resin of the cannabis plant is tetrahydrocannabinol, or THC. The other two major cannabinoids are the cannabidiols and the cannabinols. It appears that the cannabis plant first produces the mildly active cannabidiols, which are converted to the more psychoactive THCs and then broken down to relatively inactive... 

The main active ingredients of cannabis are cannabinol, cannabidiol and several isomers of tetrahydrocannabinol, of which delta-9-tetrahydro-cannabinol (THC) is probably responsible for most of the psychoactive effects of the various preparations. It is of interest to note that THC does not contain nitrogen in its three-membered ring system. The structure of THC is shown in Figure 15.8. 

Figure 15.8. Structure of tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of the cannabis plant.

Figure 19.1. Chemical structure of main active ingredient of Cannabis sativa, A9-tetrahydrocannabinol (THC) and the naturally occurring ligand for cannabinoid receptors anandamide (arachidonyl ethanolamide).

Compton, D. R., Gold, L. H., Ward, S. J., Balster, R. L., and Martin, B. R. (1992). Aminoalkylindole analogs Cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol. J. Pharmacol. Exp. Ther. 263, 1118—1126. 

Flere are the structures of the three principal tetrahydrocannabinols and of the parent, which differ mainly in chemical bonding ... 

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