Cannabinol structure

Until the mid 1960 s the only plant cannabinoid whose structure was fully elucidated was cannabinol (CBN) — a constituent which actually may represent an oxidation artifact. However, on the basis of CBN, the main cannabinoid structure skeleton became known. Thus, cannabidiol (CBD), which had been independently isolated in pure form by Adams and by Todd, was correctly assumed to be, like CBN, a terpenoid derivative attached to olivetol. But its exact structure was not elucidated. The psychoactive components of cannabis were assumed to be related tricyclic derivatives. On the basis of the tentatively elucidated constituents, Todd suggested that the cannabinoids may be formed initially in the plant by condensation of a menthatriene with olivetol. 

A second cannabis constituent, cannabidiol (CBD) was also isolated, but its structure was only partially clarified. Synthetic tetrahydro-cannabinols, which showed cannabis-like activity in animal tests, were prepared, but they obviously differed from the active natural product, on the basis of their UV spectrum. 

Mechoulam R, Gaoni Y, The isolation and structure of cannabinolic, cannabid-iolic and cannabigerolic acids. Tetrahedron 21 1223-1229, 1965. 

Jacob A, Todd AR, Cannabis indica. Part 11. Isolation of Cannabidiol from Egyptian Hashish. Observations on the Structure of Cannabinol, J Chem Soc... 

Adams R, Baker BR, Wearn RB, Structure of Cannabinol. 111. Synthesis of Cannabinol,l-Hydroxy-3-n-amyl-6,6,9-trimethyl-6-dibenzopyran, J Amer Chem Soc 62 2204-2207 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. 

Lai, S. D. and B. K. Yadav. Folk medicine of Kurushetra District (Haryana), India. EconBot 1983 37(3) 299-305. Me Phail, A. T., H. N. El Sohly, G. E. Turner and M. A. El Sohly. Stereochemical assignments for the two enantiomeric pairs of 9,10-dihydroxy-delta-6-alpha(10-alpha)-tetrahydro-cannabinols. X-ray crystal structure analysis of (DL)-trans-cannabitriol. Abstr 24th Annual Meeting American society of Pharmacognosy Univ Mississippi Oxford July 24-28 1983 ABSTR-50. 

Among the long list of diverse structures reported to possess central antitussive activity is Ahtetrahydrocannabinol (THC) [1972-08-3] (68), the principal psychoactive component of marijuana (see PSYCHOPHARMACOLOGICALAGENTS). This compound was found to be comparable to codeine against electrically induced cough in the anesthetized cat (90). Two other naturally occurring cannabinoids, cannabidiol and cannabinol, are inactive. 

A new alkaloid, which is structurally related to the cannabinols and named alfileramine (35), has been obtained from the leaves of this Rutaceous plant.34... 

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. 

The first important discovery came in 1895, when three Cambridge chemists isolated the parent molecule of the group, cannabinol, and established the family s skeleton structure. One of the three Englishmen nearly... 

Two new propyl-side-chain cannabinoids are propyl homologues of cannabi-chromene and cannabigerol. Butyl homologues of A -THC, cannabinol, can-nabidiol, and A -tetrahydrocannabinolic acid have been detected. The structure of cannabispiran (257) has been determined by X-ray analysis. By observing the... 

Fig. 1. The structures of four plant cannabinoids,zl -THC,zl -THC, cannabinol and cannabidiol...

The following abbreviations are used in the present review THC (tetrahydrocannabinol) CBD (cannabidiol) CBN (cannabinol) DMH (1,1-dimethylheptyl) SAR (structure-activity relationship) cisplatin (m-diam-minedichloroplatinum(II)) GABA (y-aminobutyric acid) MES (maximal electroshock seizures) PTZ (pentylenetetrazol) AGS (audiogenic seizure) IOP (intraocular pressure). 

Several A-ray structure determinations have been reported earlier. Cannabinoid analytical papers concerning cannabinol, " 7-... 

Canadensolide H NMR, 4, 578 Cannabichromanone synthesis, 3, 726 Cannabichromene, 3, 675 photochemistry, 3, 721 synthesis, 3, 721, 746, 748, 782 Cannabichromenic acid thermolysis, 3, 721 Cannabifuran synthesis, 4, 698 Cannabinoids biosynthesis, 3, 877 structure, 4, 548 thermolysis, 3, 721 Cannabinol occurrence, 3, 665 as pharmaceutical, 1, 151 synthesis, 3, 721, 786 Cannabinol, hexahydro-synthesis, 3, 787 Cannabinol, A -tetrahydro-occurrence, 3, 718 thermolysis, 3, 721 Cannabinol, All6-tetrahydro-metabolism, 1, 239 Cannabinol, 3,4-cis-A1,2-tetrahydro-synthesis, 3, 782... 

L., grown in India, Central America, and the United States. The plant produces a group of C21 compounds known as cannabi-noids. A total of 61 specific cannabinoids have been isolated. Although cannabinol [521-35-7] and cannabidiol [13956-29-1] are the most abundant cannabinoids, y -trans-tetrahydrocannabinol (THC) [1972-08-3] exhibits the highest psychoactivity. Cannabinol is only 5% as potent as THC, and cannabidiol is inactive. The structures of these major cannabinoids are as follows ... 

Structurally diverse cannabinoids attenuate the EFS-induced contractions with a potency order (CP 55, 940 > W1N55, 212-2 > nabilone > A - THC > cannabinol > anandamide), similar to their affinity rank order for cannabinoid CBi receptors. In addition, the selective cannabinoid CBi receptor antagonist/inverse agonist SR141716A counters the inhibitory effects of cannabinoid agonists (4). 

Around 1940, cannabinol was isolated independently by Sir Alexander R. Todd (1907-1997) at the University of Manchester and Roger Adams at the University of Illinois. However, it was determined that this compound was not responsible for the psychotropic effects of cannabis, but actually an artefact, which originated by oxidation of THC dru-ing the isolation process. [125] An additional difficulty in determining the structure of THC was, that the double bond isomerises readily in presence of acid into the thermodynamically favoru-ed 8-position. The problem of isolation was simply technical in nature in contrast to the alkaloids, which are readily purifyable by salt formation as crystalline compounds, this is not possible with /4 -tetrahydrocannabmoL... 

The amount of A °-tetrahydrocannabinol and of structurally related, nonpsychotropic compounds (e.g. cannabinol, cannabidiol and cannabidiolic acid) varies considerably. In contrast to the tropical culture forms, H. from European hemp contains little A -tetrahydrocannabinol and much cannabidiol and cannabidiolic acid. 

This is the structural class of A -THC (11), the most important cannabinoid and the main bioactive component of the psychotropic varieties of C. saliva. A -THC (11) is commonly accompanied by minor amounts of the isomer A -THC (12) and by the completely aromatized analog cannabinol (CBN, 13). Similar to cannabinodiol, CBN is thought to be an artifact and the A -THC/CBN ratio is used as an indication of the duration for which the marijuana samples are stored. 

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