Metabolic Transformation of (3R, 4R)‐Δ1(7)‐Tetrahydrocannabinol by a Rat Liver Microsomal Preparation

Binder, Michael; Barlage, Uwe

doi:10.1002/hlca.19800630126

Cited by 10 publications

(1 citation statement)

References 15 publications

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“…Metabolites extracted from the incubation mixture with mouse liver microsomes in the early work were those reported by Binder and Barlarge. 18 Although it was reasonably clear that the major This method of catalytic hydrogenation of hydroxy-THCs to the corresponding hydroxy-HHCs using rhodium/alumina provides a technique for identification of unknown hydroxy metabolites of various THCs simply by hydrogenation. The availability of hydroxy-THCs from both delta-8-and delta-9-THC enabled most of the possible hydroxy-HHCs to be synthesized and their GC/MS properties were shown to be characteristically different (Table 2), thus providing unambiguous identification.…”

Section: Metabolism Of Delta-9(1l)-thcmentioning

confidence: 99%

Electron impact-induced fragmentation of the trimethylsilyl derivatives of monohydroxy-hexahydrocannabinols

Harvey

Brown

1991

Biol. Mass Spectrom.

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Monohydroxylated derivatives of hexahydrocannabinols were synthesized by catalytic hydrogenation of hydroxytetrahydrocannabinols over a rhodium/alumina catalyst, reduction of tetrahydrocannabinol epoxides with lithium aluminium hydride, or by reaction of tetrahydrocannabinols with hydrogen peroxide. The electron impact-induced fragmentation of their trimethylsilyl ethers was investigated with the aid of deuterium labelling. Most of the compounds gave characteristically different mass spectra with abundant, diagnostically useful fragment ions. As hexahydrocannabinols containing hydroxy groups in all metabolically sensitive positions were readily prepared by the above methods, these provided reference samples for identification of new hydroxylated metabolites of isomeric tetrahydrocannabinols following hydrogenation. The method was validated by application to metabolites of delta-9(11)-tetrahydrocannabinol.

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Section: Metabolism Of Delta-9(1l)-thcmentioning

confidence: 99%

Electron impact-induced fragmentation of the trimethylsilyl derivatives of monohydroxy-hexahydrocannabinols

Harvey

Brown

1991

Biol. Mass Spectrom.

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Synthesis of cannabinoid model compounds. Part 2: (3R, 4R)‐Δ¹⁽⁶⁾‐Tetrahydrocannabinol‐5″‐oic acid and 4″(R, S)‐Methyl‐(3R, 4R)‐Δ¹⁽⁶⁾‐tetrahydrocannabinol‐5″‐oic Acid

Franke

Binder

1980

Helvetica Chimica Acta

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Two novel cannabinoid model compounds, (3 R, 4 R)-dl @)-tetrahydrocannabinol-5"-oic acid (22) and 4" (R, S)-methyl-(3 R, 4 R)-d1(6)-tetrahydrocannabinol-5"-oic acid (23) were synthesized by acid-catalyzed condensation of (+)-truns-p-mentha-2,8-dien-l-o1 (1) with the substituted resorcinols 18 and 19 obtained by a Wittig reaction between 3,5-bis (benzy1oxy)benzaldehyde (7) and methyl 4-bromobutanoate (10) or methyl 4-bromo-2 (R, 5')-methylbutanoate (11) resp. with subsequent hydrogenation. The resulting methyl esters 20 and 21 were hydrolyzed to give acids 22 and 23.In the course of our investigation of structure-activity relationships in the cannabinoid series we described the synthesis, properties and biotransformation of the non-psychotropic cannabinoid (3 R , 4 R)-d1(7)-tetrahydrocannabinol [l] [2]. We now wish to report on the synthesis of two novel cannabinoid model compounds, (3 R, 4 R)-d~f6)-tetrahydrocannabinol-5"-oic acid (22) (= ~l~(~)-THC-5"-oic acid) and 4" (R, S)-methyl-(3 R, 4 R)-Al (6)-tetrahydrocannabinol-5"-oic acid (23) ( = 4"methyl-d1 (6)-THC-5"-oic acid). Both compounds are derivatives of d1(6)-THC (3), one of the psychotropic principles of the drug hashish. Being mainly interested in acid 23 where the full aliphatic C5 side chain of the parent compound is retained, acid 22 was prepared to elaborate the synthesis of 23. Both methyl esters 20 and 21 and the acids 22 and 23 are now investigated for psychotropic activity after intraventricular injection in the cat3).The general stereospecific pathway to (3 R , 4R)-d1 @)-THC (3) and its derivatives consists according to Petrzilka et al. [3] in the acid-catalyzed reaction of (+ )-trans- ') Part 1: see [I]. 2, 3,Part of the thesis of I.F. In two double blind studies the esters 20 and 21 at doses of 10 and 20 mg resp. (spiked cigarettes, total lung delivery 2 mg 20 and 4 mg 21) could not be distinguished from placebo. 0018-019X/80/8/2508-07$01.00/0 0 1980 Schweizerische Chemische Ciesellschaft

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Microbial transformation of cannabinoids. Part 3: Major metabolites of (3R, 4R)‐Δ¹‐tetrahydrocannabinol

Binder

Popp

1980

Helvetica Chimica Acta

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The metabolic transformations of the psychotropic cannabinoid (3R, 4R)-A1tetrahydrocannabinol (5) (= A'-THC) by cultures of Fusarium nivale, Gibberella fujikuroi (both Ascomycetes) and Thamnidium elegans (Phycomycetes) were investigated. A number of metabolites, 1-4 and 6-9 were isolated from the incubations, partly purified and their structures elucidated by combined gas chromatography/mass spectrometry. Four of these metabolites, 1"-hydroxy-A'-THC (4), 2"-hydroxy-A1-THC (l), 6B-hydroxy-A'-THC (8) and 2", 6 (-dihydroxy-A'-THC (9) so far have not been reported as microbial transformation products of 5 .

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Metabolic Transformation of (3R, 4R)‐Δ¹⁽⁷⁾‐Tetrahydrocannabinol by a Rat Liver Microsomal Preparation

Cited by 10 publications

References 15 publications

Electron impact-induced fragmentation of the trimethylsilyl derivatives of monohydroxy-hexahydrocannabinols

Electron impact-induced fragmentation of the trimethylsilyl derivatives of monohydroxy-hexahydrocannabinols

Synthesis of cannabinoid model compounds. Part 2: (3R, 4R)‐Δ¹⁽⁶⁾‐Tetrahydrocannabinol‐5″‐oic acid and 4″(R, S)‐Methyl‐(3R, 4R)‐Δ¹⁽⁶⁾‐tetrahydrocannabinol‐5″‐oic Acid

Microbial transformation of cannabinoids. Part 3: Major metabolites of (3R, 4R)‐Δ¹‐tetrahydrocannabinol

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Metabolic Transformation of (3R, 4R)‐Δ1(7)‐Tetrahydrocannabinol by a Rat Liver Microsomal Preparation

Cited by 10 publications

References 15 publications

Electron impact-induced fragmentation of the trimethylsilyl derivatives of monohydroxy-hexahydrocannabinols

Electron impact-induced fragmentation of the trimethylsilyl derivatives of monohydroxy-hexahydrocannabinols

Synthesis of cannabinoid model compounds. Part 2: (3R, 4R)‐Δ1(6)‐Tetrahydrocannabinol‐5″‐oic acid and 4″(R, S)‐Methyl‐(3R, 4R)‐Δ1(6)‐tetrahydrocannabinol‐5″‐oic Acid

Microbial transformation of cannabinoids. Part 3: Major metabolites of (3R, 4R)‐Δ1‐tetrahydrocannabinol

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Metabolic Transformation of (3R, 4R)‐Δ¹⁽⁷⁾‐Tetrahydrocannabinol by a Rat Liver Microsomal Preparation

Synthesis of cannabinoid model compounds. Part 2: (3R, 4R)‐Δ¹⁽⁶⁾‐Tetrahydrocannabinol‐5″‐oic acid and 4″(R, S)‐Methyl‐(3R, 4R)‐Δ¹⁽⁶⁾‐tetrahydrocannabinol‐5″‐oic Acid

Microbial transformation of cannabinoids. Part 3: Major metabolites of (3R, 4R)‐Δ¹‐tetrahydrocannabinol