Synthetic studies of the bis-guanidinium toxin zetekitoxin AB
Abstract/Contents
- Abstract
- Zetekitoxin AB (ZTX) is a potent neurotoxin isolated from the endangered Panamanian golden frog, Atelopus zeteki. The tricyclic bis-guanidinium core of ZTX is common to other toxins such as (+)-saxitoxin (STX) and (+)-gonyautoxin II and III (GTX II, GTX III), but ZTX is one of only two known congeners with a C11-alkyl substituent. An unusual guanidinium N, O-acetal and a bridging macrolactam structure composed of a 3,4-cis-disubstituted isoxazolidine render ZTX considerably more complex than all other members of this family of bis-guanidinium natural products. The challenges encountered in efforts to synthesize ZTX from an α-hydroxyketone intermediate resulted in the design and implementation of a new synthetic route towards this complex natural product. The use of a formylpyrrole starting material enables the selective installation of a bromide at the desired C11 position. An in situ derived carbodiimide from glycine allows facile guanidine coupling of the pyrrole moiety. Diastereoselective Mannich cyclization reaction installs the requisite C13 carboxylic acid and generates a key bicyclic intermediate; from this material, the tricyclic guanidinium core is formed through oxidative dearomatization of the pyrrole ring. The tricyclic core accessed in this manner has been shown to be amenable to the synthesis of the bis-guanidinium neurotoxins STX, GTX 2, and GTX 3. The identification of cross-coupling conditions to install a suitable heterocyclic group at C11, followed by macrolactam formation with the C13 carboxylic acid, should ultimately lead to the assembly of ZTX.
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 | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Sarno, Stephen Michael |
|---|---|
| Degree supervisor | Du Bois, Justin |
| Thesis advisor | Du Bois, Justin |
| Thesis advisor | Burns, Noah |
| Thesis advisor | Wender, Paul A |
| Degree committee member | Burns, Noah |
| Degree committee member | Wender, Paul A |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Stephen Michael Sarno. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/fj614ds5383 |
Access conditions
- Copyright
- © 2021 by Stephen Michael Sarno
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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