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A Contribution to the Synthesis of Cannabinoids

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Title: A Contribution to the Synthesis of Cannabinoids
Authors: Gilles, David
Issue Date: Dec 2016
Publisher: [Honolulu] : [University of Hawaii at Manoa], [December 2016]
Abstract: Chapter 1. Cannabis, Cannabinoids, and the Endocannabinoid System. A brief background on the discovery and pharmacology of cannabinoids and of cannabinoid receptors is described. This is complemented by a summary and comparison of the cannabinoid receptor affinities of various cannabinoid ligands, and a discussion of ligand binding assays, structure activity relationships, and ligand assisted protein structure experiments, and how data from these ligand evaluation methods guide rational ligand design. Additionally, early approaches developed for the production of synthetic cannabinoids are presented and discussed as they relate to the research conducted in the Tius group.
Chapter 2. The Total Synthesis of Ketocannabinoids Revisited. The early impediment which stalled the synthesis of target cannabinoid ligands but provided a side project that culminated in the abbreviated synthesis of ketocannabinoids is discussed. Prior published work describing the previous syntheses of ketocannabinoids is presented and the challenges encountered during their improvements are described. Notably, improvements herein are applicable to the synthesis of classical, non-classical, and hybrid cannabinoid classes, and have been demonstrated through the total synthesis of enantioenriched nabilone — a highly potent cannabinoid ligand in its own right, and whose racemate is a FDA approved pharmaceutical ingredient and arguably the most iconic ketocannabinoid.
Chapter 3. The Total Synthesis of C-9 and C-11 Functionalized Classical Cannabinoids. The total synthesis of a series of C-9 and C-11 functionalized tricyclic classical cannabinoids derived from enantioenriched nabilone is described. The synthesis of target ligands was performed primarily using simple functional group manipulations and relied upon a divergent nucleophilic displacement of organoiodide intermediates. Of note are the simple reaction conditions, and benign reagents employed for these transformations. Challenges encountered during the synthesis of the eight target ligands are described as well as the solutions employed to overcome them. The pharmacological evaluation of target ligands is now charged to our collaborators at Northeastern University — the results of which will be published following completion.
Description: M.S. University of Hawaii at Manoa 2016.
Includes bibliographical references.
URI/DOI: http://hdl.handle.net/10125/51556
Appears in Collections:M.S. - Chemistry


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