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Re2O7-MEDIATED SPIROCYCLIC ETHER SYNTHESIS FROM ACYCLIC PRECURSORS: SYNTHESIS AND H2O2-MEDIATED TARGETED CELLULAR RELEASE OF A PEDERIN ANALOGUE

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 (Unpublished)

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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
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Afeke, Cephas Ofoe Dodzicoa15@pitt.educoa150000-0002-9828-8932
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFLOREANCIG, PAUL E.florean@pitt.eduflorean0000-0001-9626-3187
Committee MemberISLAM, KABIRULKAI27@pitt.eduKAI27
Committee MemberKOIDE, KAZUNORIkoide@pitt.edukoide
Committee MemberHURYN, DONNAhuryn@pitt.eduhuryn
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 2021 19:56
URI: http://d-scholarship.pitt.edu/id/eprint/41809

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