Studies toward the total synthesis of sporolide B

This dissertation presents studies directed toward the total synthesis of the marine natural product sporolide B. Chapter 1 details the isolation of sporolides A and B from the marine actinomycete Salinispora tropica and the determination of the structure of these natural products. The first chapter also reviews the proposed biosynthesis of the sporolides, including the novel halogenative Bergman-Masamune cycloaromatization reaction that is proposed to give rise to the cyclopenta[a]indane ring system. Chapter 1 concludes with Nicolaou's total synthesis of sporolide B, and the synthesis of the quinone acid fragment of the sporolides by Gademann.;Chapter 2 outlines the Smith group retrosynthefic analysis of sporolide B, as well as the first generation synthesis of the hydroquinone acid fragment. A key intermediate in the synthesis of the cyclopenta[a]indane fragment is arrived at via a Stille coupling reaction. First and second generation studies directed at the elaboration of this material toward an acyl radical mediated construction of the [3.3.0] ring system are discussed. Finally, a third generation approach completes the cyclopenta[a]indene moiety via a Nozaki-Hiyama-Kishi reaction, and the product is successfully elaborated to the target fragment.;Efforts toward the completion of sporolide B are discussed in Chapter 3. Union of the cyclopenta[a]indane and hydroquinone acid fragments is optimized and oxidation to the target quinone moiety explored. A second generation hydroquinone fragment is synthesized, coupled to the cyclopenta[ a]indane fragment, and oxidation to a quinone attempted. The cyclopenta[ a]indane fragment is modified and coupled to the hydroquinone fragment. Oxidation to the desired quinone moiety is carried out and macrocyclization attempted. The novel product of an oxidative macrocyclization reaction is isolated and the structure determined. A third generation synthesis of the hydroquinone fragment is detailed, and this fragment coupled to the cyclopenta[ a]indane fragment. Oxidation and attempts to carry out the desired macrocyclization are discussed. Chapter 3 concludes with possible future directions of the project based upon the information learned during these studies.