Studies toward the synthesis of (+)-fomannosin
Abstract/Contents
- Abstract
- Chapter 1 introduces the protoilludane class of natural products, with an emphasis on fomannosin. Fomannosin, first isolated in 1967, deviates from other members of the protoilludane family with a unique, conjugated cyclobutene moiety and in its instability to both acid and base. This natural product is reported to have phytotoxic and antimicrobial activity, most notably against Pinus tadea seedlings and Chlorella pyrenoidosa. The isolation, structural determination, and previous synthetic efforts of this phytotoxic sesquiterpene are also outlined. Chapter 2 provides an overview of a first-generation approach to fomannosin, a collaborative effort between the Maimone group at the University of California, Berkeley, and the Burns group at Stanford University. An enolate-epoxide opening reaction forms a challenging quaternary carbon of the natural product. Furthermore, a cyclization-Ramberg--Bäcklund ring contraction cascade constructs the carbon skeleton. This allows us to access methyl-ester fomannosin. Efforts to perform a late-stage reduction to provide the primary alcohol of the natural product is detailed. Chapter 3 contains an account of our extensive synthetic efforts to access the allylic alcohol. Key transformations explored in this chapter are decarboxylative oxidative eliminations as well as decarboxylative brominations. This route permits access to 2,4-dihydrofomannosin. However, we found that early construction of cyclobutene was a liability in our efforts to access fomannosin, prompting a redesign of our synthetic strategy. Chapter 4 describes an ongoing synthetic campaign to access (+)-fomannosin asymmetrically. The current second-generation synthetic strategy hinges upon two key transformations: an asymmetric allylic alkylation to form the molecule's two contiguous stereocenters, of which one is quaternary, and a late-stage Ramberg--Bäcklund ring contraction to form the final carbon-carbon bond of the fomannosin carbon skeleton. This approach assembles the fomannosin framework in fewer steps than previously reported. Ongoing efforts toward accessing the cyclopentanone ketone and the highly strained, conjugated cyclobutene are also presented.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Ordner, Ciara Mary |
|---|---|
| Degree supervisor | Burns, Noah |
| Thesis advisor | Burns, Noah |
| Thesis advisor | Du Bois, Justin |
| Thesis advisor | Maimone, Thomas |
| Degree committee member | Du Bois, Justin |
| Degree committee member | Maimone, Thomas |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Ciara Mary Ordner. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/tp227mb2293 |
Access conditions
- Copyright
- © 2022 by Ciara Mary Ordner
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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