Efficient access to bryostatin and functional bryostatin analogs : design, synthesis and evaluation of potent bryostatin analogs and the total synthesis of bryostatin 9 using B-ring annulative macrocyclization strategies
Abstract/Contents
- Abstract
- The bryostatins are a family of structurally complex natural products isolated from the marine bryozoan Bugula neritina. Bryostatin 1 is currently being investigated for cancer, Alzheimer's and HIV/AIDS indications. Despite these remarkable activities, research on the bryostatins is hampered by their low natural abundance. Efficient access by total chemical synthesis has been in large part precluded by the bryostatins' structural complexity. This dissertation describes the design, synthesis, and preliminary biological evaluation of functional bryostatin analogs that possess biological activities comparable or superior to the natural product. These fully synthetic analogs were convergently assembled in a uniquely step-economical manner using novel macrocyclization strategies, including macroacetalization and Prins-driven macrocyclization approaches. Bryostatin analogs were identified that possess unique affinities (subnanomolar) and selectivities for protein kinase C (PKC). Synthetic bryostatin analogs also exhibit subnanomolar antileukemic activity in in vitro assays. The convergent total synthesis of bryostatin 9, a highly potent congener of the natural product family, is also described.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Schrier, Adam James | |
|---|---|---|
| Associated with | Stanford University, Department of Chemistry | |
| Primary advisor | Wender, Paul A | |
| Thesis advisor | Wender, Paul A | |
| Thesis advisor | Chen, James Kenneth | |
| Thesis advisor | Du Bois, Justin | |
| Advisor | Chen, James Kenneth | |
| Advisor | Du Bois, Justin |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Adam James Schrier. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2011. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Adam James Schrier
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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