Synthesis and evaluation of novel tiglianes for PKC-related therapeutic indications
Abstract/Contents
- Abstract
- EBC-46 (aka tigilanol tiglate), has emerged as an exciting anti-cancer agent for the treatment of solid tumors. Intratumoral injection leads to activation of its primary target protein kinase C (PKC), causing increased permeability of tumor endothelial cells and subsequent inflammation to lead to tumor death. Currently, EBC-46 is obtained via extraction of blushwood tree berries, a potentially unsustainable supply tree found only in Queensland, Australia. To ensure a sustainable supply and enable further research into EBC-46, my research has focused on the development of a semi-synthesis of EBC-46 from phorbol, an abundantly available starting material. This work was since been published in Nature Chemistry and a patent has been filed. To obtain phorbol, Croton tiglium seeds are subjected to a robust extraction process that affords upwards of 10 grams of phorbol from 3 kg of seeds. With phorbol in hand, the molecule is walked though a unique oxidation sequence that yields EBC-46 in 12 % overall yield and 12 steps (> 2 grams synthesized). With a sustainable supply of EBC-46, several analogs have been synthesized to probe its structure-activity relationship with PKC. Ongoing efforts continue to elucidate how structural changes to EBC-46 influence its PKC isoform selectivity, potency, and therapeutic potential.
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 | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Fanelli, David John |
|---|---|
| Degree supervisor | Wender, Paul A |
| Thesis advisor | Wender, Paul A |
| Thesis advisor | Du Bois, Justin |
| Thesis advisor | Kanan, Matthew William, 1978- |
| Degree committee member | Du Bois, Justin |
| Degree committee member | Kanan, Matthew William, 1978- |
| Associated with | Stanford University, School of Humanities and Sciences |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | David Fanelli. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/vk126wg6658 |
Access conditions
- Copyright
- © 2023 by David John Fanelli
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