Chapter 1 . Case studies of the natural products brefeldin A, discodermolide, and nakijiquinone C are reviewed. Total synthesis, analog preparation, and biological activity studies are discussed that have given insight into structure-activity relationships.*
Chapter 2 . Previous work on the total synthesis of ilimaquinone and analogs in our laboratories is reviewed, as well as determination of the biologically active analogs. Synthetic biologically active analogs of ilimaquinone, including affinity, photoaffinity, and fluorescent analogs, support the biological target of ilimaquinone identified as S -adenosylhomocysteine hydrolase. Fluorescent labeling of the Golgi apparatus shows that the methylating agent S -adenosylmethionine reverses the biological effects of ilimaquinone.*
Chapter 3 . Synthesis of the hydrindane core of norrisolide is accomplished in four steps. The side chain of norrisolide is prepared rapidly via development of a cyclopropanation/thermal rearrangement strategy, and altering the cyclopropanation catalyst gives good enantioselectivities. A Shapiro reaction followed by addition of the hydrindane vinyllithium to the Weinreb amide of the sidechain accomplishes the key coupling step. A few more functional group manipulations have led to the diastereomer of norrisolide, and work is in progress to use a similar strategy to prepare norrisolide itself.*
*Please refer to dissertation for diagrams.
