A Total Synthesis of dl-Δ<sup>1</sup>-Tetrahydrocannabinol, the Active Constituent of Hashish<sup>1</sup>

Mechoulam, Raphael; Gaoni, Yehiel

doi:10.1021/ja01092a065

Cited by 346 publications

(131 citation statements)

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“…Perhaps Grignard reagent reacted with 6b and deprotected the hydroxyl ortho to the carbonyl to produce 6a. 25) Demethylation of 6a by BBr 3 produced 7a (81.5% yield).…”

Section: Resultsmentioning

confidence: 98%

Preparative Monohydroxyflavanone Syntheses and a Protocol for Gas Chromatography-Mass Spectrometry Analysis of Monohydroxyflavanones

Kagawa

Shigematsu

Ohta

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Flavonoids are phenolic compounds found in most plants.Since flavonoids are naturally present in fruits, vegetables, and tea, they are an integral part of the human diet.1) Ingested flavonoids are absorbed by the gastrointestinal tract and have been found in blood plasma.2) Flavonoids possess various biological and pharmacological properties, such as antioxidant activity, 3) anti-HIV-1 activity, 4) and anti-inflammatory activity. 5) They seem to protect against cancer onset, 6) vascular dementia, 7) and coronary heart disease-related deaths. 8)Flavonoids also modulate the activities of enzymes that metabolize drugs. 9) Flavonoids form the largest class of phytoestrogens known. The binding affinity of a flavonoid for the estrogen receptor primarily depends on the positions of Aand C-ring hydroxyl groups. 10) Recently, two interesting pharmacological properties of flavonoids have been reported. 1) The polymethoxyflavone, tangeretin, protects against the development of experimentally-induced Parkinson's disease in rats.11) 2) Other polymethoxyflavones inhibit the cellular excretion of certain drugs-a process mediated by P-glycoprotein.12,13) Cytochrome P450s can remove a flavonoid C-4Ј methyl and can add a hydroxyl at the C-3Ј position.14,15) To understand the diverse pharmacological effects of dietary flavonoids, their metabolic pathways must be known.A previous study of ours 16) showed that both rat and human cytochrome P450s convert flavanones to the corresponding 2,3-trans-flavanonols and flavones; whereas, only the human enzyme can convert the flavanone to isoflavone. We also recently reported a procedure for the specific deuteration of flavanones.17) With these deuterated flavanones as substrates, we determined that, most likely, the initial step in flavanone P450-catalyzed metabolism is abstraction of a hydrogen radical from the C-2 or -3 position of the flavanone skeleton.After rats received flavanone via a stomach tube, the most common urinary metabolites found were those with the C-4 ketone reduced and those with hydroxyls added at positions C-3 and C-6.18) Another P450 metabolic study found that aromatic hydroxylation products, flavones, unusual quinoltype oxidation products, chromone derivatives, and flavan-4-ol derivatives were produced when several different flavanones were substrates.19) Therefore, although all flavonoids have a common three-ring skeleton, it appears that ring substituents determine the metabolic fate of a specific substrate.If demethylated and hydroxylated flavonoid P450 metabolic products, amongst others, are to be unequivocally characterized, their physical properties must be compared with known standards. Previously, we reported a synthetic procedure for (Ϯ)-2,3-trans-flavanonols, which are hydroxylated at the C-3 position.20,21) Consequently, only those compounds could be unquestionably identified as P450 metabolic products during our previous study. 16) In order to identify other metabolic monohydroxyflavanones, we have now developed procedures to synthetically produce these co...

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“…Perhaps Grignard reagent reacted with 6b and deprotected the hydroxyl ortho to the carbonyl to produce 6a. 25) Demethylation of 6a by BBr 3 produced 7a (81.5% yield).…”

Section: Resultsmentioning

confidence: 98%

Preparative Monohydroxyflavanone Syntheses and a Protocol for Gas Chromatography-Mass Spectrometry Analysis of Monohydroxyflavanones

Kagawa

Shigematsu

Ohta

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…After the completion of THC synthesis in 1964 by Raphael Mechoulam [20] and the identified of cannabinoid receptors CB 1 [21] and CB 2 in 1980s [22], the interest in synthesising cannabinoids has increased to the yield of more than 100 substances. SCs contain a great variety of structurally dissimilar compounds and this makes the classification of SCs is quite complex.…”

Section: Pharmacological and Toxicological Aspects Of Synthetic Cannamentioning

confidence: 99%

Bioanalytical methods for the determination of synthetic cannabinoids and metabolites in biological specimens

Aldlgan

Torrance

2016

TrAC Trends in Analytical Chemistry

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Recently the use of synthetic cannabinoids (SCs) has increased around the world. As a result, the importance for accurate analysis of SCs in human biological matrices is evident and continues to be especially challenging due to their chemical structures being constantly modified. Many methods have been published recently for the analysis of SCs in human biological samples. This review provides an overview of the analytical methods used for the analysis of SCs and their metabolites in biological specimens with a special focus on chromatographic analysis and sample preparation.Liquid chromatography assay is the most commonly used for confirmation purposes of SCs and their metabolites in biological matrices. In blood and oral fluid, analysis of SCs must be very sensitive. In urine, SCs have extensive metabolism pathways; therefore the main target compounds are their hydroxyl and carboxyl metabolites, which is important to recognise when establishing clinical and forensic toxicology analytical methods.

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“…Sodium metal is used to form the phenoxide in the differentially protected hydroquinone 3a and resorcinol (11). The phenoxide of 3a refluxed with prenyl bromide affords the prenylated phenol 10 smoothly in 85% yield.…”

Section: Phenoxide Ortho-c-alkylationmentioning

confidence: 99%

Strategies for the Preparation of Differentially Protectedortho-Prenylated Phenols

Hoarau¹,

Pettus²

2002

Synlett

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A new process for ortho-prenylation of phenols is presented within the context of known methods. All of the processes are briefly assessed with regards to the substitution patterns and accompanying functional groups tolerated by each strategy. The conclusion reached is that a new procedure using ortho-quinone methides, for which an experimental protocol is provided, offers the greatest generality and flexibility in the preparation of ortho-prenylated phenol derivatives.

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A Total Synthesis of dl-Δ¹-Tetrahydrocannabinol, the Active Constituent of Hashish¹

Cited by 346 publications

References 1 publication

Preparative Monohydroxyflavanone Syntheses and a Protocol for Gas Chromatography-Mass Spectrometry Analysis of Monohydroxyflavanones

Preparative Monohydroxyflavanone Syntheses and a Protocol for Gas Chromatography-Mass Spectrometry Analysis of Monohydroxyflavanones

Bioanalytical methods for the determination of synthetic cannabinoids and metabolites in biological specimens

Strategies for the Preparation of Differentially Protectedortho-Prenylated Phenols

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A Total Synthesis of dl-Δ1-Tetrahydrocannabinol, the Active Constituent of Hashish1

Cited by 346 publications

References 1 publication

Preparative Monohydroxyflavanone Syntheses and a Protocol for Gas Chromatography-Mass Spectrometry Analysis of Monohydroxyflavanones

Preparative Monohydroxyflavanone Syntheses and a Protocol for Gas Chromatography-Mass Spectrometry Analysis of Monohydroxyflavanones

Bioanalytical methods for the determination of synthetic cannabinoids and metabolites in biological specimens

Strategies for the Preparation of Differentially Protectedortho-Prenylated Phenols

Contact Info

Product

Resources

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A Total Synthesis of dl-Δ¹-Tetrahydrocannabinol, the Active Constituent of Hashish¹