Studies toward the total synthesis of spirastrellolide A

Chapter one of this dissertation describes background into the biological properties of spirastrellolide A (SA) as a potent and selective protein phosphatase inhibitor. It then goes on to provide information on the isolation, structural elucidation, and structural features of SA. Additionally, it compares SA to other natural products with similar biological activity.;Finally, chapter one ends with a literature review of synthetic work on SA and the other known spirastrellolides. By highlighting the total syntheses of spirastrellolide A methyl ester by Paterson and spirastrellolide F methyl ester by Furstner an overview of synthetic challenges, strategies, and methods is seen. Other synthetic progress on the spirastrellolides is also briefly acknowledged.;Chapter two provides a detailed account of my spirastrellolide A synthetic progress. It begins by analyzing synthetic challenges inherent to SA. Then my hypothesized synthetic plan for a total synthesis of SA is outlined. Synthetic advancement toward specific fragments of the SA carbon chain is discussed. It covers strategies employed for building the carbon framework of the molecule while installing necessary stereocenters.;As chapter two continues, studies toward the synthesis of four distinct fragments of SA are explored. A synthesis of the C41--C 47 side chain is explained. The C33--C40 fragment synthesis is also described. Next, the synthesis of stereospecific chlorohydrin containing molecules is examined. Finally, the progress toward a synthesis of the C1--C16 fragment is described in detail. The synthesis of this fragment focuses partially on the incorporation of methodology previously developed in the Chamberlin laboratory to install a cis-tetrahydropyran ring and an anti -1,3-diol moiety. The chapter concludes with suggested work.;Chapter three provides all of the necessary information and data to repeat the work reported in chapter two. It begins with experimental procedures for synthesizing each of the key intermediates mentioned in successful synthetic routes. Each experimental procedure is followed by experimental data. Finally, chapter three is followed by an appendix with 1H and 13C NMR spectra useful for identifying key molecular structures.