Part I. Total synthesis of (-)-cylindrocyclophane A: Exploring the reversible nature of the olefin cross-metathesis reaction. Part II. Total synthesis of (+)-13-deoxytedanolide and progress toward the total synthesis of tedanolide

This two part dissertation describes the total syntheses of (−)-cylindrocyclophane A, a C2-symmetric naturally occurring [7,7]-paracyclophane, and (+)-13-deoxytedanolide, a potent antitumor marine macrolide. Part I, chapter one provides an introduction to the cylindrocyclophane family of natural products. Specifically, the isolation, structure elucidation, biosynthetic origin, and biological activity of the cylindrocyclophanes are discussed. Furthermore, relevant synthetic approaches toward the cylindrocyclophanes are delineated.* The second chapter of Part I describes the total synthesis of (−)-cylindrocyclophane A via a cross olefin metathesis dimerization cascade. The dimerization substrate was accessed via Danheiser annulation, which employed a siloxyalkyne available from Kowalski homologation of the appropriate ester.* The final chapter of Part I explores the reversible nature of olefin metathesis as it pertains to the exclusive formation of the [7,7]-paracyclophane skeleton. Molecular modeling and experimental evidence support the theory that a cascade of reversible olefin metatheses drives the reaction to the [7,7]-paracyclophane skeleton.* Part II of this dissertation discusses the first total synthesis of (+)-13-deoxytedanolide and efforts toward (+)-tedanolide. Chapter one introduces the tedanolide family and details the isolation, structural elucidation, and impressive biological activity of (+)-tedanolide and (+)-13-deoxytedanolide. In addition, relevant synthetic approaches by other research groups toward the tedanolides are summarized.* Part II, chapter two introduces the synthetic strategy envisioned for the synthesis of the tedanolides. The synthetic plan entails a unified approach to both (+)-tedanolide and (+)-13-deoxytedanolide that calls for the late-stage introduction of the trisubstituted epoxide and employs a dithiane-vinyl iodide linchpin.* Chapter three of Part II describes the construction of the carbon skeletons of (+)-tedanolide and (+)-13-deoxytedanolide via union of the elaborated linchpin with the requisite epoxide and iodide fragments.* In addition, this chapter details the development of a novel oxidation strategy, which employs the Evans-Tishchenko reaction to access the seco-acid of (+)-13-deoxytedanolide, and ultimately leads to the completion of the first total synthesis of (+)-13-deoxytedanolide.* *Please refer to dissertation for diagrams