Author

Abhisek Ray

ORCID Identifier(s)

0000-0002-0088-0576

Graduation Semester and Year

2016

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Carl Lovely

Abstract

Our group is primarily interested in the total synthesis of oroidin-based pyrrole-imidazole-containing marine sponge-derived alkaloids. These pyrrole-imidazole natural products are a growing class of alkaloids with exotic connectivity, unique topologies, and high nitrogen content. Presence of 2-aminoimidazole and pyrrolecarboxamide fragments in the structure represent their signature features. Due to their structural diversity and biological activity, many groups are interested in the total synthesis of these natural products. It has been proposed that many of the alkaloids in this family are produced in nature by dimerization of the simplest member, oroidin. In this dissertation we have explored a biosynthetic hypothesis disclosed by Scheuer and coworkers in their report of the isolation of palau’amine. In this context total synthesis of axinellamine A in the first instance. This dissertation consists of two parts. The first part specifically addresses a problem pertaining to the installation of a key functional group (chlorine) that had presented a significant roadblock for us. In this context a preliminary investigation was undertaken based on a cycloaddition, postcycloaddition functionalization strategy and accordingly a variety of oxidative methods were explored for accomplishing this goal. Unfortunately, while a number of different reaction pathways were observed, none of them were productive as far as our synthetic goals were concerned. An alternative approach involving a precycloaddition functionalization, cycloaddition strategy was undertaken which was successful. In this alternative strategy a functional group (Br, I, SiMe2Ph) was introduced in the diene component of the Diels-Alder precursor that can serve a surrogate for chlorine. A number of potential functionalization chemistries were explored and in this process a number of heterosubstituted vinylimidazoles were prepared from the corresponding propargyl alcohol by hydrosilylation, hydroalumination/halogenation. These vinylimidazole derivatives were then evaluated in intermolecular Diels-Alder reaction with N-phenylmaleimide (NPM), forming tetrahydrobenzimidazole derivatives. In some cases the aromatized DA adduct was isolated and in others the initial DA adduct i.e. an enamine was isolated, depending on the N-protecting present in vinylimidazole. The second part of this dissertation describes studies towards a total synthesis of architecturally complex oroidin dimers, in particular axinellamine A. Novel silylsubstituted vinylimidazoles were extensively used in this context. These studies revealed a concise entry into the all trans-substituted spiro cyclopentyl imidazolone system comparable to that found in axinellamine A and related natural products. These structures are accessed through an intramolecular DA reaction of a silyl containing enyne followed by an oxidative rearrangement. Further studies are on going to elaborate the fully functionalized DA adduct and to improve the yield and selectivity of some of the described transformations.

Keywords

Intramolecular and intermolecular Diels-Alder of vinylimidazoles, Hydrosilylation, Oxidative rearrangement

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

Included in

Chemistry Commons

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