Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor's Name

David A. Becker

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Stanislaw F. Wnuk

Second Advisor's Committee Title

committee member

Third Advisor's Name

Kevin O'Shea

Third Advisor's Committee Title

committee member

Fourth Advisor's Name

Anthony P. DeCaprio

Fourth Advisor's Committee Title

committee member

Fifth Advisor's Name

Richard A. Bone

Fifth Advisor's Committee Title

committee member

Keywords

Synthesis, Azasteroids, Azasteroidal mimics, Azulenes, Azulenyl nitrones, Pseudoazulenes, Pseudoazulenyl nitrones

Date of Defense

12-7-2016

Abstract

Steroids are one of the essential classes of bioactive compounds and are involved in many biological functions which include their role as signaling compounds, the alteration of membrane fluidity and the regulation of a variety of metabolic processes. In order to identify novel compounds with beneficial pharmacological action, the synthesis of modified steroids is gaining much attention in recent years. Among those analogs, azasteroids are one of the most important classes which display a variety of biological activities, often free from undesirable side effects. The challenges in the synthesis of steroids, particularly azasteroids, and the potential of azasteroids as novel drugs has prompted numerous investigations in this field. The synthetic methods leading to steroidal derivatives (azasteroids) with one or more nitrogen atoms are very limited. Generally, oxidative cleavage of the steroidal rings is needed to introduce nitrogen atom(s) in order to synthesize azasteroids.

In the first part of this dissertation, explorations into the synthetic methods needed for making a new steroidal A-ring or seco A-ring on a tricyclic benz[e]indenedione (a dimer compound obtained in connection with continued work on the study of anhydrobases of the isoxazole series) were pursued. In this process, a series of three tricyclic hydrazone compounds have been designed and synthesized to mimic the tetracyclic rigid core structure of azasteroids. We are eager to ascertain if these compounds possesses any interesting biological properties.

In continued research on the synthesis of azulenyl and pseudoazulenyl nitrones, (to target ROS generation at the site of mitochondria), the second part of this research was aimed at the synthesis of cationic pseudoazulenyl nitrones with mitochondriotropic properties. Several pseudoazulenyl nitrone derivatives were synthesized using the natural compound valtrate, obtained from the roots of Centranthus ruber. Unfortunately, the attempts made to convert these compounds into the corresponding cationic pseudoazulenyl nitrones failed. However, an interesting pseudoazulenyl dinitrone molecule bearing an imidazole group was prepared. Also, a pseudoazulenyl mono nitrone compound with an electron donating group was synthesized by leaving a highly reactive aldehyde functionality intact for further use in synthetic study.

Identifier

FIDC001734

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