6 1-Tetrahydrocannabinolic acids

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. 

Kanter, S. L., M. R. Musumeci and L. E. Hollister. Quantitative determination of delta9-tetrahydrocannabinol and delta9-tetrahydrocannabinolic acid in marihuana by high-pressure liquid chromatography. J Chromatogr 1979 171 504. 

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. " ... 

In the 1970s the biosynthesis of cannabinoids was investigated with radiolabeling experiments. 14C-labeled mevalonate and malonate were shown to be incorporated into tetrahydrocannabinolic acid and cannabichromenic acid at very low rates (< 0.02%). Until 1990 the precursors of all terpenoids, isopentenyl diphosphate and dimethyl-allyl diphosphate were believed to be biosynthesized via the mevalonate pathway. Subsequent studies, however, proved that many plant terpenoids are biosynthesized via the recently discovered deoxyxylulose phosphate pathway (Eisenreich et al., 1998 Rohmer, 1999). It was shown that the Cio-terpenoid moiety of cannabinoids is biosynthesized entirely or predominantly (>98%) via this pathway (Fellermeister et al., 2001). The phenolic moiety is generated by a polyketide-type reaction sequence. 

The oxidocyclization of cannabigerolic acid to tetrahydrocannabinolic acid is catalyzed by tetrahydrocannabinolic... 

The psychoactive ingredients of cannabis sativa are finally formed when its leaves are dried at elevated temperature so that e.g. tetrahydrocannabinolic acid is decarboxylated to A9-THC. 

Irradiation of several members of the cannabinoid family has provided useful routes to some derivatives. Cannabichromene (576) is converted into cannabicyclol (577) when it is irradiated in r-butyl alcohol-acetone <71JCS(C)796) and tetrahydrocannabinolic acid (578) is aromatized to cannabinolic acid (579) (70CPB1327). 

Strong bases (amphetamines, methamphetamine, procaine), bases of medium strength (cocaine, heroin, noscapine, quinine), weak bases (diazepam, methaqualone), strong acids (A-9-tetrahydrocannabinolic acid), moderately strong acids (phenobarbi-tal) and weak acids (A-9-tetrahydrocannabinol) can be separated in a single run along with neutral solutes (testosterone, testosterone propionate). However, in order to... 

Acidic and basic drugs (phenobarbital, diazepam, methaqualone, testosterone, cannabinol, testosterone propionate, 9-tetrahydro-cannabinol, 9-tetrahydrocannabinolic acid) CEC Hypersil C8 Acetonitrile-50 mAf phosphate buffer, pH 2.5 (60 40) with 2 pl/ml hexylamine for 1 min, then linear gradient to acetonitrile-25 mM phosphate buffer with 2 pl/ml hexylamine (75 25) 340 mm x 100 pm i.d. 250 mm to the detector, stepped gradient, comparison with MECC... 

The X-ray crystal structure of A1 -tetrahydrocannabinolic acid B is reported,362 and one of the previously reported (Vol. 4, p. 75) dihydrobenzofurans from the citric acid-catalysed condensation of orcinol with menth-4-en-3-ol is shown to be (256) by X-ray analysis.363 G.c.-m.s. assay of A -THC-OMe allows the detection of 1 ng mP1 plasma of A -THC.364 The mass spectral fragmentation of A -THC, A6-THC, and some isomeric cannabinoids to the prominent m/e 231 ion has been examined.365 Miniaturized syntheses of 32 natural, or potentially natural, cannabinoids are reported in connection with their chromatographic analysis.366... 

Figure 7 CEC step gradient of basic, neutral, and acidic compounds. Initial conditions (for first minute) acetonitrile/25 mM phosphate buffer pH 2.5 (60/40) with 2-mL/min hexylamine. Final conditions acetonitrile/25 mM phosphate buffer pH 2.5 (75/25) with 2-mL/min hexylamine. A voltage of 25 kV and a temperature of 20°C was used. Analytes (i) phenobarbital, (j) diazepam, (I) testosterone, (m) cannabinol, (n) testosterone propionate, (o) A9-tetrahydrocannabinol, and (p) A9-tetrahydrocannabinolic acid. (Reprinted from Ref. 46, with permission.)...

A -Tetrahydrocannabinol A -Tetrahydrocannabinol Tetrahydrocannabivaric Acid Cannabicyclol Cannabichromene Tetrahydrocannabinolic Acid... 

Tetracycline hydrochloride, 1005 Tetracycline methylenelysine, 714 Tetradecyltrimethylammonium bromide, 439 Tetraethylammonium bromide, xvii Tetraethylthiuram disulphide, 566 Tetraethylthiuram monosulphide, 788 Tetrafluorodichloroethane, 532 Tetrahydroacridinylamme, 1000 Tetrahydroaminacrine, 1000 A -Tetrahydrocannabinol, 424 A -Tetrahydrocannabinol, 423 Tetrahydrocannabinolic acid, 424 Tetrahydrocannabinoloic acid, 425 Tetrahydrocannabivaric acid, 217 Tetrahydrocannabivarin, 217 Tetrahydrocortisol, 666 Tetrahydrocortisone, 666... 

In order to identify cannabis products, one of the most frequently used methods is gas chromatography-mass spectrometry (GC-MS). The identification relies on the presence of A -THC, CBD and CBN in the sample, and to a lesser extent, the presence of A -THC (the isomer of the active principle of cannabis) and A -tetrahydrocannabinolic acid. The following presents a method that has been found to work, although there are a number of similar methods reported in the literature [9], The sample is prepared for GC-MS analysis as follows ... 

Stanaszek, R., Zuba, D. A comparison of developed and validated chromatographic methods (FIPLC, GC MS) for determination of delta-9-tetrahydrocannabinol (5 -TFIC) and delta-9-tetrahydrocannabinolic acid (5 -TFICA-A) in hemp. Probl. Forensic Sci. 71, 313-322 (2007)... 

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... 

C]MVA, [l- H]geraniol, and [l- H]nerol were all incorporated into can-nabichromenic acid (120) and tetrahydrocannabinolic acid (121) by Cannabis sativa, and [car oxy- CJcannabigerolic acid (122) labelled these two compounds and also cannabidiolic acid (123). The results probably show that cannabigerolic... 

Zeeuw, R.A. de et al. A -Tetrahydrocannabinolic Acid, an Important Component in the Evaluation of Cannabis Products. Journal of Pharmacy and Pharmacology 24 (1972) 1. 

The structure of A -THC was built from the structure of A -tetrahydrocannabinolic acid B as determined by X-ray crystallography. THC analogues were modelled by modifying the basic structure. Aminoalkylindoles and azoles were subject to conformational analysis in order to select initial low energy conformations for all molecules. 

Rosenqvist, E. and Ottersen, T. (1975). The crystal and molecular structure of delta-9-tetrahydrocannabinolic acid b. Acta Chem. Scand. B., 29 379-384. 

Cannabis is by far the most commonly used illicit drug. Most people who abuse hard drugs such as heroin also abuse cannabis. Tetrahydrocannabinol (acid and A -metabolite) is regulated in the German traffic law (see Table 7-1), and amphetamine, opiates (morphine) and cocaine (as benzoylecgonine metabolite) are also mentioned. 

An example of a CEC analysis of an illicit drug was shown by Lurie and collaborators [134], In this study, a standard mixture of seven cannabinoids was separated, and this test mixture was then compared with concentrated hashish and marijuana extracts (Figure 5.26). The cannabinoid standards used were cannabigerol (CBG), cannabidiol (CBD), cannabinol (CBN), A-9-tetrahydrocannabinol (d9-THC), A-8-tetrahydrocannabinol (d8-THC), cannabichromene (CDB), and A-9-tetrahydrocannabinolic acid (d9-THCA-A), with dimethyl sulfoxide (DMSO) as the neutral marker. A Hypersil C18 column (3 (im dp) was used. The column inner diameter was 100 pm and had a total length of 49 cm, and the effective length was 40 cm. UV detection was conducted at 210 nm. The run buffer was 75% ACN and 25% 25 mM phosphate buffer pH 2.57. The applied voltage was 30 kV, and the column temperature was kept at 20°C. 

Further cannabinoids are /d -tetrahydrocannabinolic acids A and B, which contain an additional carboxylic acid function at C-2 or C-4. [124] By smoking of cannabis these undergo decarboxylation and therefore raise the THC level (Fig. 5.66). 

The formation of cannabidiolic acid and cannabichromenic acid takes place independently on other oxidoreductases. Cannabidiolic acid is the main can-nabinoid in fibre hemp. Cannabichromenic acid is also produced in drug hemp. In contrast to other cannabinoids, it is produced as a 5 1 mixture of enantiomers. Therefore, seen from the genetic standpoint, the expression of the cannabidiolic acid synthase or of the tetrahydrocannabinolic acid synthase determines if the phenotype correlates with drug or fibre hemp. 

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