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Title:Dearomative hydroboration-enabled synthesis of idarubicinone and synthesis of minor cannabinoids and their metabolites
Author(s):Dennis, David Gerald
Director of Research:Sarlah, David
Doctoral Committee Chair(s):Sarlah, David
Doctoral Committee Member(s):Denmark, Scott E.; White, M. Christina; Silverman, Scott K.
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Dearomatization
Arenophile
Total Synthesis
Cannabinoids
Cannabis
Hydroboration
CBD
Abstract:Anthracyclines are archetypal representatives of tetracyclic type II polyketide natural products that are widely used in cancer chemotherapy. Although syntheses of this class of compounds have been extensively explored, all known approaches are based on annulations, relying on the union of properly pre-functionalized building blocks. To complement these studies, here we showcase an alternative, non-annulative entry to anthracyclines, starting from a polynuclear arene. Specifically, tetracene was converted to idarubicinone, an aglycone of the FDA approved anthracycline idarubicin, by a judicious orchestration of Co- and Ru-catalyzed arene oxidation and a novel dearomative hydroboration. This global functionalization strategy, a combination of site-selective arene- and dearomative-functionalizations, provided the key anthracycline framework in five operations and enabled rapid and controlled access to idarubicinone. Another class of compound deriving from polyketide synthases are the cannabinoids. Having a long history of use, yet controversial nature Cannabis offers the possibility for the treatment of many diseases. Reports are varied, however, possibly due to the affect of numerous and under-studied minor cannabinoids. A small library of minor cannabinoids were prepared and tested for their anti-inflammatory pain with the goal of discovering a novel lead compound. Specifically, cannabimovone was prepared in biomimetic fashion and displayed a remarkable ability to stimulate the production of cytokines in a BV-2 mouse microglial cell line under inflammatory response.
Issue Date:2021-06-21
Type:Thesis
URI:http://hdl.handle.net/2142/113121
Rights Information:Copyright 2021 David Dennis
Date Available in IDEALS:2022-01-12
Date Deposited:2021-08


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