Hashish. 20. Synthesis of (.+-.)-.DELTA.1- and .DELTA.6-3,4-cis-cannabidiols and their isomerization by acid catalysis

Gr, Handrick; Rk, Razdan; Db, Uliss; Hc, Dalzell; Boger, Eliahu

doi:10.1021/jo00435a007

“…While the effects of the trans-CBD enantiomers and their 7-OH and 7-COOH metabolites on various components of the endocannabinoid system and other targets have been studied, [84][85][86][87][88] there are no pharmacological data on cis-CBD, that is the (R,S)-or (S,R)-CBD isomers. [89][90][91] The impact of chirality on sodium ion channel pore binding of PHT-related 5-(cyclo)alkyl-5-phenylhydantoins has been discussed. 59…”

Section: Resultsmentioning

confidence: 99%

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites: Insights from Molecular Modeling

Ujváry¹,

Lopata²

2019

Preprint

0

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<div> Cannabidiol (CBD), a nonpsychotropic constituent of <i>Cannabis sativa</i>, has recently been approved by the US FDA for the treatment of certain forms of pediatric epilepsy. The mechanism by which CBD exerts its antiepileptic effects, however, is not known. Herein we describe the results of molecular modeling studies comparing the stereoelectronic properties of phenytoin (PHT) with those of CBD and its carboxylic acid metabolite, as well as of 7-hydroxycannabidivarin. Also, the cyclohexenecarboxylic acid core of 7-COOH-CBD perfectly mimics the unsaturated bioactive metabolite of the commonly used antiepileptic valproic acid was also noted. We propose that C–7 oxidized phytocannabinoid metabolites are involved in the phenytoin-like anticonvulsant effects of the parent phytocannabinoid drugs.</div>

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“…While the effects of the trans-CBD enantiomers and their 7-OH and 7-COOH metabolites on various components of the endocannabinoid system and other targets have been studied, [77][78][79][80] there are no pharmacological data on cis-CBD, that is the (R,S)-or (S,R)-CBD isomers. [81][82][83] The impact of chirality of PHT-related 5-(cyclo)alkyl-5-phenylhydantoins on sodium ion channel pore binding has been discussed. 53…”

Section: Resultsmentioning

confidence: 99%

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites Insights from Molecular Modeling

Ujváry¹,

Lopata²

2018

Preprint

0

View full text Add to dashboard Cite

<div> Cannabidiol (CBD), a nonpsychotropic constituent of <i>Cannabis sativa</i>, has recently been approved by the US FDA for the treatment of certain forms of pediatric epilepsy. The mechanism by which CBD exerts its antiepileptic effects, however, is not known. Herein we describe the results of molecular modeling studies comparing the stereoelectronic properties of phenytoin (PHT) with those of CBD and its carboxylic acid metabolite, as well as of 7-hydroxycannabidivarin. Also, the cyclohexenecarboxylic acid core of 7-COOH-CBD perfectly mimics the unsaturated bioactive metabolite of the commonly used antiepileptic valproic acid was also noted. We propose that C–7 oxidized phytocannabinoid metabolites are involved in the phenytoin-like anticonvulsant effects of the parent phytocannabinoid drugs.</div>

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“…12 : SOCl 2 (6 drops) was added to an ice-cold solution of alcohol 11a (78.4 mg, 0.224 mmol) in 2.09 mL of dry pyridine. After 15 min, the solution was allowed to warm to rt, then diluted with brine and extracted twice with ether and twice with ethyl acetate.…”

Section: Methodsmentioning

confidence: 99%

High-Pressure Diels−Alder Cycloadditions between Benzylideneacetones and 1,3-Butadienes: Application to the Synthesis of (R,R)-(−)- and (S,S)-(+)-Δ⁸-Tetrahydrocannabinol

Ballerini

¹

,

Minuti

²

,

Piermatti

³

2010

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High-pressure Diels-Alder reactions of various alkoxy/alkyl-substituted benzylideneacetones with methyl-1,3-butadienes are reported. Activation by high pressure (8-11 kbar) in combination with the mild Lewis acid HfCl(4).2THF allows these reactions to efficiently and regioselectively produce a series of ortho-substituted cyclohexenyl-benzene cycloadducts, that are useful precursors for the expeditious construction of the privileged 6,6-dimethyltetrahydro-6H-benzo[c]chromene skeleton. Application to the synthesis of Delta(8)-trans-THC in both enantiomeric pure forms is based on the successful resolution of selected cycloadduct by the SAMP-hydrazone method.

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Hashish. 20. Synthesis of (.+-.)-.DELTA.1- and .DELTA.6-3,4-cis-cannabidiols and their isomerization by acid catalysis

Cited by 19 publications

References 1 publication

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites: Insights from Molecular Modeling

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites: Insights from Molecular Modeling

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites Insights from Molecular Modeling

High-Pressure Diels−Alder Cycloadditions between Benzylideneacetones and 1,3-Butadienes: Application to the Synthesis of (R,R)-(−)- and (S,S)-(+)-Δ⁸-Tetrahydrocannabinol

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Hashish. 20. Synthesis of (.+-.)-.DELTA.1- and .DELTA.6-3,4-cis-cannabidiols and their isomerization by acid catalysis

Cited by 19 publications

References 1 publication

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites: Insights from Molecular Modeling

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites: Insights from Molecular Modeling

Towards Understanding the Phenytoin-like Antiepileptic Effect of Cannabidiol and Related Phytocannabinoid Metabolites Insights from Molecular Modeling

High-Pressure Diels−Alder Cycloadditions between Benzylideneacetones and 1,3-Butadienes: Application to the Synthesis of (R,R)-(−)- and (S,S)-(+)-Δ8-Tetrahydrocannabinol

Contact Info

Product

Resources

About

High-Pressure Diels−Alder Cycloadditions between Benzylideneacetones and 1,3-Butadienes: Application to the Synthesis of (R,R)-(−)- and (S,S)-(+)-Δ⁸-Tetrahydrocannabinol