Cannabis synthesis

CS182 Crombie, L., W. M. L. Crombie and S. V. Jamieson. Extractives of Thailand cannabis Synthesis of canniprene and... 

Cannabinol, A -3,4-trans-tetrahydro-biological activity, 3, 877 Cannabinol, (—)-A -3,4- ran5-tetrahydro-as pharmaceutical, 1, 151 Cannabinolic acid synthesis, 3, 721 Cannabinolic acid, tetrahydro-photochemistry, 3, 721 Cannabis, citrylidene-, 3, 675 Cantharidin synthesis, 1, 440 Capillarin occurrence, 3, 677 ozonolysis, 3, 681... 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

After identification of A9-THC as the major active compound in Cannabis and its structural elucidation by Mechoulam and Gaoni in 1964 [66], a lot of work was invested in chemical synthesis of this substance. Analogous to the biosynthesis of cannabinoids, the central step in most of the A9-THC syntheses routes is the reaction of a terpene with a resorcin derivate (e.g., olivetol). Many different compounds were employed as terpenoid compounds, for example citral [67], verbenol [68], or chrysanthenol [69]. The employment of optically pure precursors is inevitable to get the desired (-)-trans-A9-THC. 

Szirmai M (1995) Total synthesis and analysis of major human urinary metabolites of dl-tetrahydrocannabinol, the principal psychoactive component of Cannabis sativa L. Dissertation, Uppsala University, Sweden... 

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. 

Ghosh R, Todd AR, Wilkinson S, Cannabis indica. Part v. The synthesis of cannabinol, / Soc, 1393-1396, 1940. 

Biotransformation of (+)- and -)-cis/trans- etheno s to (-f)-verbenone has been achieved by a cell-free system of Cannabis sativa Callus.The (—)- and (+)-verbenone (via verbenol) were the starting materials for the first synthesis of the (—)- and (+)- enantiomers of A -tetrahydrocannabinol. 

A -3,4-cis-THC has now been found in Cannabis sativa (Phenotype III) other papers reporting the characterization of compounds from Cannabis sativa concern conclusive identification and synthesis of cannabinodiol, " which is known to result from the photochemical irradiation of cannabinol (Vol. 7, p. 51), and the identification of A -tetrahydrocannabinolic acid " and (+)-cannabitriol (263) " (263) and the corresponding C-2 ethyl ether may be epoxide-derived. " ... 

Ghosh, R., Todd, A.R., and Wilkinson, S. Cannabis indlca. Part IV. The synthesis of some tetrahydrodlbenzopyran derivatives. 

The opium alkaloids codeine and morphine served as models for the synthesis of naloxone, an important analog used to treat and diagnose opiate addicts, and also led to the discovery of endogenous opioids (enkephalins and endorphins) (see Chapter 47). Similarly, A9-tetrahydro-cannabinol (THC), the component of Cannabis sativa responsible for the central nervous system (CNS) effect, has also been found to reduce nausea associated with cancer chemotherapy (see Chapter 18). 

Aiylation with a homocuprate. A key step in a synthesis of the cannabis constituent 4 is the reaction of 1 with the homocuprate derived from olivetol dimethyl ether (2) hy regiospecific lithiation followed by reaction with CuBr. The cuprate does not react with 1 in the absence of a Lewis acid, but in the presence of BF, etherate (3.5 equiv.) ( —)-3 is obtained in 78% yield with high regio- and stereospecificity. The dihydrobromide of... 

Each route of synthesis will result in an impnrity profile which can be analysed. Unlike cannabis, heroin and cocaine, the impnrities are present in very low concentrations and need to be extracted from the amphetamine matrix. Liquid-liquid extraction (LLE) and solid-phase extraction (SPE) have been most frequently applied for this pnrpose [13-16]. Of these, LLE is currently the most widely used technique. In addition, there are attempts being made to develop the method so that it can be optimized to allow data exchange between different laboratories (in different countries) [17]. 

The most comprehensive account of synthetic work in the field is contained in three full papers from Crombie s group. Most of this work has already appeared in note form. The first paper deals with the condensation of citral with phloro-glucinols in general then comes the reaction specifically with olivetol (338). The products from the reaction in pyridine are citrylidenecannabis (340) and cannabichromene (341), which occurs in Cannabis. The latter is further converted either by heating in pyridine, or, better, by u.v. irradiation in acetone, to cannabicyclol (342), whose structure was established, and which had already been shown to be present in Cannabis. If the synthesis is carried out with a... 

Delta-9-THC is the main active constituent extracted from Cannabis sativa (Tuner, 1985 in Marijuana 1984, Ed. Harvey, DY, IRL Press, Oxford). Numerous articles have described not only psychotropic effects of cannabinoids but also their influence on the immune function [Hollister L. E., J. Psychoact. Drugs 24 (1992) 159-164]. The majority of in vitro studies have shown that cannabinoids have immunosuppressant effects inhibition of the mitogen induced proliferative responses of T lymphocytes and B lymphocytes [Luo, Y. D. et ah, Int. J. Immuno-pharmacol. (1992) 14,49-56 Schwartz, H. et at., J. Neuroimmunol. (1994) 55,107-115], inhibition of the activity of cytotoxic T cells [Klein et at., J. Toxicol. Environ. Health (1991) 32, 465-477], inhibition of the microbicidal activity of macrophages and of TNF-a synthesis [Arata, S. et at.. Life Sci. (1991) 49, 473-479 Fisher-Stenger et al., J. Pharm. Exp. Then (1993) 267, 1558-1565] and inhibition of the cytolytic activity and the TNFa production of large granular lymphoc3rtes [Kusher et al.. Cell. Immun. (1994) 154, 99-108],... 

Burstein S, Hunter SA, Latham V, Mechoulam R, Melchior DL, RenzuUi L, Tefft RE Jr (1986) Prostaglandins and cannabis XV. Comparison of enantiomeric cannabinoids in stimulating prostaglandin synthesis in fibroblasts. Life Sci 39 1813-1823... 

Desarnaud F, Cadas H, Piomelli D (1995) Anandamide amidohydrolase activity in rat brain microsomes. Identification and partial characterization. J Biol Chem 270 6030-6035 Deutsch DG, Chin SA (1993) Enzymatic synthesis and degradation of anandamide, a cannabi-... 

The alterations produced by THC and other cannabinoids in biogenic amine levels as well as on uptake, release and synthesis of neurotransmitters and effects on enzymes have been the subject of numerous investigations (for reviews see [8,52,55,114,115]). It is beyond the scope of the present summary to try to analyse and put into a proper perspective the wealth of data published so far. It is our subjective view that the mode of action of cannabi-mimetic compounds is somehow directly associated with prostaglandin metabolism (see, in particular, the series of papers by Burstein [115,116]), and/or reduction of hippocampal acetylcholine turnover observed in rats [117,118]. The latter effect is enantiospecific and follows the known SAR of the cannabinoids. This in vivo selectivity of action suggests that the THC may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septalhippocampal pathway. 

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