Total syntheses of (+)- and (-)-cacospongionolide B: Investigation into structural requirements for phospholipase A(2) inhibition

Chapter 1. Natural products containing the γ-hydroxybutenolide moiety, important pharmacophores, are reviewed, and their structures and biological activities are discussed. The syntheses of important γ-hydroxybutenolide natural products are reviewed to develop an understanding of the synthetic methods useful in their preparation.; Chapter 2. The total syntheses of cacospongionolide B (1) and its enantiomer are described. The pivotal transformations in their preparation include a three-step reaction sequence that couples the two fragments of the natural product and generates the dihydropyran ring.*; Chapter 3. The synthesis of cacospongionolide E, and several structural variants of cacospongionolide B are described. A brief review on the role of secretory phospholipase A₂ in the inflammation process in given, and initial biological results from the inhibition of bee venom secretory phospholipase A₂ are described.; *Please refer to dissertation for diagrams.