ERA

Download the full-sized PDF of New Aspects of Nazarov Reaction: Additive Effects, Gold Catalysis and Application Toward the Synthesis of TaxinineDownload the full-sized PDF

Analytics

Share

Permanent link (DOI): https://doi.org/10.7939/R3Q38F

Download

Export to: EndNote  |  Zotero  |  Mendeley

Communities

This file is in the following communities:

Graduate Studies and Research, Faculty of

Collections

This file is in the following collections:

Theses and Dissertations

New Aspects of Nazarov Reaction: Additive Effects, Gold Catalysis and Application Toward the Synthesis of Taxinine Open Access

Descriptions

Other title
Subject/Keyword
Nazarov
Taxinine
Gold Catalysis
Prions
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Joy, Shaon
Supervisor and department
Dr. West, Frederick (Chemistry)
Examining committee member and department
Dr. Zhang, Liming (Chemistry)
Dr. Clive, Derrick (Chemistry)
Dr. Klobukowski, Mariusz (Chemistry)
Dr. Lowary, Todd (Chemistry)
Dr. Cairo, Christopher (Chemistry)
Department
Department of Chemistry
Specialization

Date accepted
2013-06-05T11:47:43Z
Graduation date
2013-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Methods involving efficient and stereoselective carbon-carbon bond formation enable chemists to synthesize bioactive natural products and drugs. The Nazarov reaction is a versatile tool for the construction of functionalized cyclopentenones. This 4π-electrocyclization provides easy and efficient access to multi-substituted cyclopentenones with excellent stereocontrol at two contiguous ring carbons and opportunities to link to additional bond-forming events. Typically, the Nazarov cyclization involves 1,4-pentadien-3-ones. However, development of unconventional initiation protocols to access the key pentadienyl cation in the Nazarov reaction has gained considerable popularity over the past decade. Chapter 1 describes the recent activity in the area of alternate activation protocols for Nazarov cyclization. One rapidly expanding area of homogeneous gold catalysis is the Au(I) catalyzed rearrangements of propargylic carboxylates, leading to domino reaction sequences. Chapter 2 discusses the synthesis of bridged bicyclic enynyl acetates and their use as dienone surrogates. The compounds undergo a [3,3]-rearrangement followed by a 4π-electrocyclization under Au(I) catalysis to form cyclopentenones in a regioselective fashion. Chapter 3 recounts our comprehensive investigation on the effects of additives in the silicon-directed Nazarov cyclization. We have found that the presence of hydroxylic additives can lead to facile and clean cyclizations of β-silyl substituted dienones. Successful cyclization of some lightly substituted dienones have been reported, which are otherwise highly unreactive under standard conditions. In chapter 4 our continued efforts toward the synthesis of taxinine are reported. The completion of the synthesis requires a six-membered ring annulation method to a previously established bicyclo[5.3.1]undecene core. Our attempts at the six-membered ring annulation involving a late-stage C-H insertion via metal-carbenoid chemistry has been presented. Some novel reactivities of the late-stage intermediates have also been explored. Prion diseases are a group of infectious neurodegenerative disorders that affect both humans and animals. They are invariably fatal due to the lack of proper treatment or cure. Current research relies heavily on the hypothesis that prion pathogenesis coincides with the cellular prion protein (PrPC) undergoing conformational change to the β-sheet enriched isoform PrPSc. Chapter 5 elaborates our efforts in the development of multivalent PrPSc binding compounds. Three classes of compounds were synthesized and tested for anti-prion activity.
Language
English
DOI
doi:10.7939/R3Q38F
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Scadeng, O.; Wu, Y.-K.; Fradette, R. J.; Joy. S.; West, F. G. “The Nazarov Cyclization,” In Comprehensive Organic Synthesis, 2nd Ed.; Molander, G. A.; Knochel, P. Eds.; Elsvier; Vol. 5, in press.Mays, C. E.; Joy, S.; Li, L.; Yu, L.; Genovesi, S.; West, F. G.; Westaway, D. Biomaterials 2012, 33, 6808.

File Details

Date Uploaded
Date Modified
2014-06-05T07:00:03.361+00:00
Audit Status
Audits have not yet been run on this file.
Characterization
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 11669118
Last modified: 2015:10:12 11:41:41-06:00
Filename: SJOY-PhD-THESIS-CHEMISTRY-FALL2013.pdf
Original checksum: f4698d888430e85a343e5a003941471e
Well formed: true
Valid: false
Status message: Invalid page tree node offset=11664712
Status message: Outlines contain recursive references.
File title: SJ-THESIS-Title Page-CORRECTED
Activity of users you follow
User Activity Date