Dearomative hydroboration-enabled synthesis of idarubicinone and synthesis of minor cannabinoids and their metabolites

Dennis, David Gerald

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https://hdl.handle.net/2142/113121 Copy

Description

Title

Dearomative hydroboration-enabled synthesis of idarubicinone and synthesis of minor cannabinoids and their metabolites

Author(s)

Dennis, David Gerald

Issue Date

2021-06-21

Director of Research (if dissertation) or Advisor (if thesis)

Sarlah, David

Doctoral Committee Chair(s)

Sarlah, David

Committee Member(s)

• Denmark, Scott E.
• White, M. Christina
• Silverman, Scott K.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(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.

Graduation Semester

2021-08

Type of Resource

Thesis

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http://hdl.handle.net/2142/113121

Copyright and License Information

Copyright 2021 David Dennis

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