Author

Ravi P. Singh

ORCID Identifier(s)

0000-0002-2900-5855

Graduation Semester and Year

2019

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Carl Lovely

Abstract

Our group is mainly interested in the total synthesis of marine sponge-derived 2-aminoimidazole-containing alkaloids. A new family of 2-aminoimidazole alkaloids, the Leucetta alkaloids, is a group of >60, 2-aminoimidazole natural products found in marine sponges. Our lab is also interested in the total synthesis of oroidin-based pyrrole-imidazole containing marine sponge-derived alkaloids. These natural products are a growing class of alkaloids with exotic connectivity, unique topologies, and high nitrogen content. The presence of 2-aminoimidazole and pyrrolecarboxamide fragments in their framework represent the signature structural features. Recently, these secondary metabolites have received substantial attention because of their challenging structures and strong biological activities. This dissertation consists of two parts. The first part specifically addresses a problem pertaining to the total synthesis of two family members of Leucetta alkaloids; spirocalcaridines A and B through the development of a novel method for the de novo construction of imidazole ring. Specifically, hypervalent iodine (III) mediated oxidative dearomatizing spirocyclization of propargyl guanidines was developed to construct the complete skeletal core present in spirocalcaridine A and B. A survey of the reactivity of these advanced intermediates was undertaken in an effort to complete the total synthesis. While significant advancements were uncovered, the completion of the total synthesis remain to be accomplished. Also, while exploring this transformation, a number of novel reactions were developed. Chapter 2 discusses the development of an unusual one-pot N-cyanation-spirocyclization reaction of propargyl amines leading directly to the spiro-fused cyclohexadienone. Chapter 3 focuses on the development of tandem thioacylation-intramolecular hydrosulfenylation of propargyl amines to access 2-aminothiazolidines. The second part discusses the utilization of a more traditional approach by functionalizing an existing imidazole ring for the completion of the total synthesis of two oroidin family members; hymenin and 2-debromohymenin. A convenient 9-step synthesis of these pyrroloazepinone containing natural products from a commercially available iodoimidazole via a key gold-catalyzed hydroarylation was achieved. Elaboration of the pyrroloazepinone through reduction, C2-azidation delivered the key late stage intermediates. Chemoselective reduction of the C2-azide and reductive cleavage of N-methoxy group with molybdenum hexacarbonyl delivered the two hymenin congeners in good yield.

Keywords

Leucetta, Oroidin, Spirocalcaridine, Total synthesis, Hymenin, Stevensine

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

Included in

Chemistry Commons

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