Stereospecific functionalization of vicinal dihalides and efforts toward the total synthesis of archaeal lipids
Abstract/Contents
- Abstract
- Chapter 1 shows that while nucleophilic substitution reactions are universally taught, they are often much more complicated than we think. A huge amount of work has been done to understand neighboring-group participation in SN1-type reactions both in a qualitative and quantitative sense. Studying the reactivity of dibromides and their surrogates led to important insights in physical organic chem-istry. However, the enantiospecificity and potential synthetic use of such processes are underexplored. Chapter 2 is a reprint of a review I coauthored entitled "Chiral Alkyl Halides: Un-derexplored Motifs in Medicine". While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and me-dicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biologi-cal systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this chapter that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Chapter 3 demonstrates that dihalides could be used to generate a configurational-ly stable bromonium ion either through Lewis acid activation or by using a strongly ionizing solvent. This bromonium ion can then be trapped by a host of nucleophiles inter- and intramolecularly. Using this strategy, a variety of natural products and natural product relevant motifs were synthesized in our laboratory. Chapter 4 describes the importance of studying archaeal lipids and the ongoing efforts toward their total syntheses. Archaeal lipids are structurally unique, their biosynthesis has several unanswered questions, and their biophysical properties have not been studied on pure compounds. Our work describes a highly convergent strat-egy toward GDGT-0, which exploits the molecule's C2 symmetry. We have shown the feasibility of a key enantioselective hydrogenation step, and alternative strategies have been described that may circumvent certain challenges.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Gal, Balint | |
|---|---|---|
| Degree supervisor | Burns, Noah | |
| Thesis advisor | Burns, Noah | |
| Thesis advisor | Trost, Barry M | |
| Thesis advisor | Wender, Paul A | |
| Degree committee member | Trost, Barry M | |
| Degree committee member | Wender, Paul A | |
| Associated with | Stanford University, Department of Chemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Bálint Gál. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Balint Gal
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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