Persistent Link:
http://hdl.handle.net/10150/184033
Title:
SYNTHESIS OF DELTA-3-CANNABIDIOL AND THE DERIVED RIGID ANALOGS.
Author:
NAGARAJA, KODIHALLI NANJAPPA.
Issue Date:
1987
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Synthesis of 2- 1-cyclohexene-5-methyl-2-(1-methyl-ethenyl)-1-yl -1,3-diacetyl-5-(n-pentyl)resorcinol and the related delta-3-cannabidiol analogs, with modification of the terpenoid and/or the aliphatic side chain, were successfully carried out to study the structure anticonvulsant activity relationship. Modifications of the terpenoid skeleton and the sidechain were done by the initial condensation of suitable a β-keto ester with appropriate resorcinol carrying the required side chain to obtain benzpyrones as the starting compounds. Attempts were made to synthesize the conformationally rigid delta-1-cannabidiol (delta-1-CBD) analogs through inter- and intramolecular Diels-Alder strategy. The expected products, ethyl-1-methyl-10-[1-phenyl-2,6-diacetyl-4-(n-pentyl)]-2,3,4,5,6,7,8-octahydro-naphthalene-4-carboxylate and the corresponding stereo- and/or regioisomers were observed to form in trace amounts in presence of Lewis acid catalyst. Cyclization to the corresponding delta-3-THC, in case of diene 55, was a major drawback. The parent dienes 55 and 55A, were seen to decompose and generate high molecular weight products. The diene 55 and 55LA were inert to thermal Diels-Alder reactions. Attempts to obtain the diacrylate of the triol -2-[1-cyclohexene-2-(1-hydroxy-1-methylethyl)-1-yl]-5-(n-pentyl)-resorcinol, to setup the molecule for intramolecular Diels-Alder reaction met with little success. The delta-3-CBD analogs (55, 58, 61, 65, 66, and 67) were submitted for pharmacological activity tests to provide information on the structure-anticonvulsant activity. The anticonvulsant activity was assessed employing the audiogenic seizure (AGS) susceptible rat model of epilepsy and the standard rotorod (ROT) paradigm to evaluate differential neurotoxicity. The results of these tests are encouraging in the n-pentyl analog 55, while the results of analogs 58, 61 with n-pentyl side chain and 65, 66, 67 with dimethylheptyl side chain are awaited.
Type:
text; Dissertation-Reproduction (electronic)
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmaceutical Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Martin, Arnold R.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleSYNTHESIS OF DELTA-3-CANNABIDIOL AND THE DERIVED RIGID ANALOGS.en_US
dc.creatorNAGARAJA, KODIHALLI NANJAPPA.en_US
dc.contributor.authorNAGARAJA, KODIHALLI NANJAPPA.en_US
dc.date.issued1987en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractSynthesis of 2- 1-cyclohexene-5-methyl-2-(1-methyl-ethenyl)-1-yl -1,3-diacetyl-5-(n-pentyl)resorcinol and the related delta-3-cannabidiol analogs, with modification of the terpenoid and/or the aliphatic side chain, were successfully carried out to study the structure anticonvulsant activity relationship. Modifications of the terpenoid skeleton and the sidechain were done by the initial condensation of suitable a β-keto ester with appropriate resorcinol carrying the required side chain to obtain benzpyrones as the starting compounds. Attempts were made to synthesize the conformationally rigid delta-1-cannabidiol (delta-1-CBD) analogs through inter- and intramolecular Diels-Alder strategy. The expected products, ethyl-1-methyl-10-[1-phenyl-2,6-diacetyl-4-(n-pentyl)]-2,3,4,5,6,7,8-octahydro-naphthalene-4-carboxylate and the corresponding stereo- and/or regioisomers were observed to form in trace amounts in presence of Lewis acid catalyst. Cyclization to the corresponding delta-3-THC, in case of diene 55, was a major drawback. The parent dienes 55 and 55A, were seen to decompose and generate high molecular weight products. The diene 55 and 55LA were inert to thermal Diels-Alder reactions. Attempts to obtain the diacrylate of the triol -2-[1-cyclohexene-2-(1-hydroxy-1-methylethyl)-1-yl]-5-(n-pentyl)-resorcinol, to setup the molecule for intramolecular Diels-Alder reaction met with little success. The delta-3-CBD analogs (55, 58, 61, 65, 66, and 67) were submitted for pharmacological activity tests to provide information on the structure-anticonvulsant activity. The anticonvulsant activity was assessed employing the audiogenic seizure (AGS) susceptible rat model of epilepsy and the standard rotorod (ROT) paradigm to evaluate differential neurotoxicity. The results of these tests are encouraging in the n-pentyl analog 55, while the results of analogs 58, 61 with n-pentyl side chain and 65, 66, 67 with dimethylheptyl side chain are awaited.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmaceutical Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMartin, Arnold R.en_US
dc.identifier.proquest8711643en_US
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