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

Sponges of the major class, Calcarea can be found in nearly all marine habitats. Two Calcarea genera, Leucetta and Clathrina have found be rich with 2-aminoimidazole alkaloids. The first alkaloid of these groups was isolated in 1987 from a bright yellow sponge of the class Calcispongiae (calcarea) and Leucetta chagosensis dendy (Leucetta) collected near Na'ama in the Gulf of Eilat (Aqaba) in the Red Sea. The nomenclature for this whole series of compounds is based on the location of the initial source material. The first Chapter describes the isolation, biological activities, possible biosyntheses and total synthesis of these alkaloids. The last section of this Chapter describes the retrosynthetic approach to three of these alkaloids, calcaridine A, spirocalcaridine A and spirocalcaridine B via oxidative reaction of corresponding 4,5-dibenzylicimidazole derivatives. The second Chapter describes the studies of oxidative reactions of Davis, Aryl N-sulfonyloxaziridine with tetrahydrobenzimidazole (THB) derivatives to provide corresponding spiro-fused 5-imidazolones or in some cases bis-addition products, depending on the nature of the 2-substituent and the solvent employed. The comparison of oxidative abilities of DMDO and oxaziridine is also described later in this Chapter, and it has been found that while stereoselectivity of both reagents are the same, oxaziridine shows relatively slow reactivity towards complex molecules thereby requiring higher reaction time probably due to the steric clashes between the oxidant and the reductant. It has also been found that both DMDO and oxaziridine can be used for the oxidative addition of imidazole derivatives to synthesize corresponding dihydroxy imidazolidines. In Chapter three, total synthesis of (±)-epi-calcaridine A and (±)-calcaridine A is described using position selective metalations of 4,5-diiodo-1-methyl-1H-imidazole to provide a 14-methoxynaamine A derivative, which was subjected to oxidative rearrangement with 3-(4-nitrophenyl)-2-phenylsulfonyloxaziridine to construct the imidazolone core of calcaridine A, and this was the first examples of rearrangements involving substrates other than a tetrahydrobenzimidazole type derivative. In addition to the total synthesis, relative stereochemistry of the natural product has been determined through X-ray crystal structure of the epimeric congener. Total syntheses of six other Leucetta derived alkaloids, preclathridine A, clathridine A, naamidine G, 14-methoxynaamidine G, naamine G and naamidine H are described in Chapter four, by extrapolation of the approach described in the second Chapter. In these two chapters we demonstrated that 4,5-dihaloimidazoles can be functionalized in a sequential and controlled manner in the order of C5 &rarr C4 &rarr C2 using Grignard reagents (for the 4- and 5-positions) and n-BuLi (for C2). The studies described in the fifth Chapter are directed toward the total synthesis of spirocalcaridine A and B. Several approaches developed based on the biosynthetic consideration, starting from 4,5-diiodoimidazole and ipso-cyclization of 4-aryl trienone via de novo synthesis of imidazole ring, are described in this Chapter.

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

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