Graduation Year

2023

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Edward Turos, Ph.D.

Committee Member

Kirpal Bisht, Ph.D.

Committee Member

Jianfeng Cai, Ph.D.

Committee Member

Jill Roberts, Ph.D.

Keywords

reduction, acylated, silylated, protected hydroquinone, one-pot, enzymatic, stability

Abstract

Quinones are compounds containing cyclohexadiene diones and can be found in a variety of biological systems. Quinones participate in redox cycling to initiate the formation of free radicals which contributed to their overall biological activity. When quinones are reduced by either biological or chemical reductants, they can become unstable and undergo autoxidation back to their quinoidal form. One way to avoid autoxidation is the use of protected hydroquinones. Many protected hydroquinones in literature have been shown to be efficient in drug delivery as probes or molecular containers or they can act like prodrugs to be released into active forms to act upon a selected biological target. These protected hydroquinones are underutilized for chemical synthesis. Chapter one of this manuscript discusses p-quinone characteristics in chemical and biological systems as well as their reduced and protected hydroquinones. This chapter provides an overview of the types of quinone reductions, their instabilities, biological targets that reduce quinones, types of one-pot reactions, and protected hydroquinones and their biological activity. The second chapter focuses on the one-pot zinc mediated reductive acylation of doxorubicin and other electron rich p-quinones that can access protected hydroquinones. The third chapter discusses other protecting groups for hydroquinones, achieved by the one-pot zinc-mediated reductive silylation of electron-rich quinones. The fourth chapter describes the chemical and enzymatic stabilities of these newly synthesized protected hydroquinone derivatives. This will provide insight to their prodrug capabilities by enzymatic activation and their potential as drug delivery systems.

Included in

Chemistry Commons

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