Synthetic efficiency through strategic design : (I) the design and development of novel reactivity regenerating reagents for step economy, (II) the supply-impacting total synthesis of bryostatin 1
Abstract/Contents
- Abstract
- Organic synthesis as a discipline is driven at the delivery of high-value molecular entities as research tools, therapeutic agents, reagents, and materials. The simple delivery of these entities, however, does not constitute a successful synthetic effort. Instead, synthetic chemists are in constant pursuit of ideal syntheses that minimize step counts, waste, and development and delivery time; yet maximize chemical yield, safety, and purity and quantity of the resulting outputs. Presented in this defense will be three strategies aimed at this overall goal of efficient synthetic strategies. First, the design and development of 1,2,3-butatriene equivalents will be discussed, including their enabling application to the synthesis of a novel class of staurosporine-inspired kinase inhibitors using a [5+2]/[4+2] tandem cycloaddition sequence. Using a related reactivity regeneration strategy, the second story in this defense demonstrates the scalable synthesis of a new solvatochromic fluorophore enabled by the development of two new tetramethyleneethane equivalents. Finally, a scalable and supply-impacting synthesis of the marine macrolide bryostatin 1, a lead compound for the treatment of Alzheimer's disease and cancer, as well as for the eradication of HIV/AIDS, will be described. This synthesis represents a solution to the supply of bryostatin 1 and related analogs and enables further clinical and academic research on the potential of these transformative PKC modulators. Overall, these three stories serve as a demonstration of how strategic design strategies can contribute to the overall synthetic efficiency and economy of a synthetic sequence.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Jeffreys, Matthew S |
|---|---|
| Associated with | Stanford University, Department of Chemistry. |
| Primary advisor | Wender, Paul A |
| Thesis advisor | Wender, Paul A |
| Thesis advisor | Kanan, Matthew William, 1978- |
| Thesis advisor | Waymouth, Robert M |
| Advisor | Kanan, Matthew William, 1978- |
| Advisor | Waymouth, Robert M |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Matthew S. Jeffreys. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Matthew Scott Jeffreys
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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