Record Details

Development of a synthetic strategy toward trans-Cyclobutane-Containing natural products: enantioselective total synthesis of (+)-Psiguadial b / Lauren Marie Chapman ; Sarah E. Reisman, advisor.
Pasadena, California : California Institute of Technology, 2017.
1 online resource (xxii, 363 leaves) : digital (34 Mb), illustrations (some color).
CIT theses ; 2016
Trans-cyclobutane-containing meroterpenoids are a structurally intriguing class of natural products with a diverse array of pharmacologically interesting properties. Herein, the development of a synthetic strategy for de novo construction of the trans-cyclobutane motif is described, which has enabled the first enantioselective total synthesis of the cytotoxic natural product, (+)-psiguadial B. Specifically, we have developed a photochemical Wolff rearrangement with tandem catalytic, asymmetric addition to a ketene generated in situ. To our knowledge, this work represents the first example of this methodology used to prepare enantioenriched amides. A palladium-catalyzed, directed C(sp3)â€"H alkenylation reaction is used to quickly build molecular complexity, and two distinct epimerization strategies permit access to either enantiomer of the natural product from a single enantiomer of organocatalyst. In the course of this work, three different synthetic routes toward (+)-psiguadial B were investigated and each is discussed. These studies have led to the execution of several challenging key transformations, including an ortho-quinone methide hetero-Diels-Alder cycloaddition with a cyclohexanone-derived enol ether, a vinyl sulfide-mediated Prins cyclization, and a modified Norrishâ€"Yang cyclization. Ultimately, the successful synthetic strategy was realized by employing a ring-closing metathesis to form the strained, 7-membered terpene framework, and a late-stage benzylic oxidation/arylation strategy to complete the core of the natural product. Finally, in an effort to apply these key strategy concepts in the context of other bioactive trans-cyclobutane-containing natural products, initial results toward a concise total synthesis of (+)-rumphellaone A are presented.
Advisor and committee chair names found in the thesis' metadata record in the digital repository.
Dissertation note:
Thesis (Ph. D.) -- California Institute of Technology, 2016.
Bibliography, etc. note:
Includes bibliographical references.
Linked resources:
Caltech Connect
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 Record created 2017-11-20, last modified 2017-11-21

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