Studies toward the enantioselective synthesis of briarane diterpenes
Abstract/Contents
- Abstract
- First isolated over fifty years ago, the briaranes are a diverse family of approximately 800 diterpenoid natural products that are unified by a unique carbon skeleton which houses a trans-[8.4.0]-tetradecane ring system. This natural product family collectively possesses a broad range of interesting bioactivity and several unusual structural features, such as halogen-bearing stereocenters. This, in combination with the presence of multiple highly conserved structural features has attracted the attention of synthetic chemists for the last three decades. Despite considerable effort, no successful synthesis of any member of this family has been reported in the literature. At the outset of our work, the reports toward these natural products focused largely on the synthesis of structural motifs, rather than targeting the synthesis of any specific member. A synthesis which succeeded in establishing these important motifs in a streamlined manner as well as incorporating the rest of the carbon skeleton was completely unknown. Our group targeted a representative member, (+)-briareolide J, for synthesis, with the goal that the successful development of a route toward this member would enable the synthesis of other structurally related members which differ only by oxidation state. We developed a first-generation approach toward these natural products which hinged on the convergent coupling of two fragments using an enantioselective aldol reaction. Further elaboration of this coupled product enabled the installation of important structural motifs while incorporating necessary functionality to complete the synthesis. Ultimately, we found that our final disconnection was not able to establish the challenging trans-[8.4.0]-tetradecane ring system, leading us to revise our synthetic strategy. Targeting a redesigned second-generation synthesis, we developed a radical-polar crossover reaction to couple two enantioenriched fragments, establishing an array of important structural motifs in a single step. Further elaboration of this intermediate afforded an advanced precursor containing all the carbon atoms needed to complete the synthesis. However, we once again found that this intermediate was incapable of forming the trans-[8.4.0]-tetradecane ring system through our planned disconnection. Lastly, model studies helped to establish possible root causes of these challenges, prompting us to once again redesign our synthetic strategy. Although ultimately unsuccessful, the insights from these studies pave the way for future synthetic endeavors.
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 | Farr, Joshua Daniel |
|---|---|
| Degree supervisor | Burns, Noah |
| Thesis advisor | Burns, Noah |
| Thesis advisor | Chen, James Kenneth |
| Thesis advisor | Du Bois, Justin |
| Degree committee member | Chen, James Kenneth |
| Degree committee member | Du Bois, Justin |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Joshua Daniel Farr. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/tn062kh5033 |
Access conditions
- Copyright
- © 2022 by Joshua Daniel Farr
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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