Afeke, Cephas Ofoe Dodzi
(2021)
Re2O7-MEDIATED SPIROCYCLIC ETHER SYNTHESIS FROM ACYCLIC PRECURSORS: SYNTHESIS AND H2O2-MEDIATED TARGETED CELLULAR RELEASE OF A PEDERIN ANALOGUE.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
The synthesis of spirocyclic ethers from acyclic precursors bearing ketones that are flanked by an allylic alcohol and an alkene in the presence of Re2O7 via a sequence of allylic alcohol transposition, oxocarbenium ion formation, and Prins cyclization is described. The method is atom economical and results in significant increases in molecular complexity, with multiple stereocenters being set relative to a stereocenter in the substrate.
The use of self-immolative linkers in stimulus-responsive release of organic molecules and biological effectors demonstrate utility for the development of prodrugs and other therapeutics. This project describes the total synthesis of a pederin analogue (10-demethoxy-13-O-methyl pederin) which has shown cytotoxicity towards a number of cancer cells. Subsequent borylation of the analogue at the C7-hydroxy substituent via a new borylation strategy afforded a small molecule biological agent which leverages the unique hydrogen peroxide environment of cells under oxidative stress to release the cytotoxic pederin analogue, thereby providing an opportunity for future advancements in anticancer therapy.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
8 October 2021 |
| Date Type: |
Publication |
| Defense Date: |
23 July 2021 |
| Approval Date: |
8 October 2021 |
| Submission Date: |
17 September 2021 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
189 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Re2O7, rhenium oxide, spirocyclization, spirocyclic ethers synthesis, pederin analogue synthesis, H2O2-mediated targeted release |
| Date Deposited: |
08 Oct 2021 19:56 |
| Last Modified: |
08 Oct 2022 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41809 |
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