Graduation Semester and Year

2010

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Carl Lovely

Abstract

This dissertation consists of two parts. The first part describes the synthesis of northern fragment of nagelamide R and the enantioselective total synthesis of cyclooroidin. The oroidin family of marine natural products is a growing group of marine sponge-derived alkaloids which contain 2-aminoimidazole and pyrrolecarboxamide fragments as their signature features. The structural complexity, and in many cases interesting biological profiles, of these compounds has rendered several of these natural products as targets of interest. In the context of nagelamide R, the key transformation involves the intramolecular cyclization of a pyrrolecarboxamide via the carbonyl oxygen leading to the formation of oxazoline, whose subsequent elaboration by pyrrole bromination and imidazole azidation provides the fully functionalized northern fragment of the natural product. This chemistry suggests a possible biosynthetic pathway to the formation of nagelamide R through nagelamide B via activation and substitution of the amide carbonyl. The key steps en route to the enantioselective total synthesis of cyclooroidin involve a coupling reaction between an imidazole chlorohydrin and pyrrole 2-carboxylic acid followed by intramolecular cyclization to form an oxazine ring. Conversion into the corresponding pyrazine, followed by bromination of the pyrrole and introduction of the azide group at the C-2 position of the imidazole provided the complete natural product framework. Removal of the protecting group and reduction of the azide to amine provide synthetic enantioselective cyclooroidin. The second part of this dissertation describes studies towards some oroidin dimers including palau'amine and ageliferin. These studies have resulted in a concise entry into the all trans-substituted spiro cyclopentyl imidazolone system found in palau'amine and related natural products. These structures are accessed through an intramolecular Diels-Alder reaction of an enyne followed by an oxidative rearrangement. The final section describes a preliminary investigation of methods for the stereoselective incorporation of the chloro moiety, which is present in several oroidin dimers, including palau'amine.

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

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