Synthesis and Use of Selenonic Acids as Epoxidation Catalysts and Mechanistic Investigation of the Antioxidant Drug Ebselen

Sands, Kai Neil

Synthesis and Use of Selenonic Acids as Epoxidation Catalysts and Mechanistic Investigation of the Antioxidant Drug Ebselen

dc.contributor.advisor	Back, Thomas George
dc.contributor.author	Sands, Kai Neil
dc.contributor.committeemember	Derksen, Darren
dc.contributor.committeemember	Ling, Chang-Chun
dc.contributor.committeemember	Gailer, Jurgen
dc.contributor.committeemember	Gravel, Michel
dc.date	2023-11
dc.date.accessioned	2023-08-14T21:06:21Z
dc.date.available	2023-08-14T21:06:21Z
dc.date.issued	2023-08
dc.description.abstract	Selenium and selenium dioxide have long been known to effect the oxidation of organic substrates, first appearing in the early 20th century as a method of dehydrogenating hydrocarbons. Little progress was made in the use of organoselenium reagents in organic synthesis until the early 1970’s when the selenoxide syn-elimination was shown to be a general method for the installation of double bonds. This reinvigorated the field of organoselenium chemistry, and over the ensuing decade several new selenium-mediated oxidations were developed, including the epoxidation and dihydroxylation of alkenes, Baeyer-Villiger oxidations and the oxidation of phenols to quinones. Many studies of these reactions have invoked a peroxyseleninic acid as the active oxidant, though little evidence was provided at the time to support these claims. Contrary to these early reports, we found that the peroxyseleninic acid is a relatively poor epoxidizing agent due to its facile decomposition to a mixed selenonium-selenonate salt. This salt is stable in the solid state, but generates the corresponding selenonic acid in the presence of hydrogen peroxide. The selenonic acid itself is inactive towards epoxidations; however, in the presence of excess peroxide, rapid epoxidation occurs. This shows that the selenonic acid must be further activated, presumably to the benzeneperoxyselenonic acid. Although selenonic acids were first reported more than a century ago, they have been studied far less frequently and have found little application as synthetic reagents when compared to their seleninic acid analogues. This is in large part due to difficulties in their preparation and characterization, which led to errors in their structure identification in earlier work. Given the newfound importance of selenonic acids in oxidation reactions, a new protocol for the efficient and expedient synthesis of selenonic acids was needed. This was achieved in a one-pot reaction starting from readily available aryl bromides to furnish a range of aryl selenonic acids bearing electron-donating and -withdrawing groups in good to high yields. Finally, organoselenium compounds can mimic the selenoenzyme glutathione peroxidase, which protects cells against oxidative stress by reducing peroxides in the presence of the tripeptide thiol glutathione. Ebselen is arguably the most studied such mimetic; however, there is still considerable uncertainty in its mechanism of action. The final portion of this thesis is a systematic reinvestigation of several key reactions of the proposed catalytic cycles in order to gain further insight into its mechanism which may allow for the design of better glutathione peroxidase mimetics.
dc.identifier.citation	Sands, K. N. (2023). Synthesis and use of selenonic acids as epoxidation catalysts and mechanistic investigation of the antioxidant drug Ebselen (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/116857
dc.identifier.uri	https://dx.doi.org/10.11575/PRISM/41699
dc.language.iso	en
dc.publisher.faculty	Science
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Organoselenium chemistry
dc.subject	Antioxidants
dc.subject	Ebselen
dc.subject	Selenonic acids
dc.subject	Oxidation
dc.subject	Epoxidation
dc.subject	Peroxides
dc.subject	Benzeneperoxyselenonic aicd
dc.subject	Benzeneperoxyseleninic acid
dc.subject.classification	Chemistry--Organic
dc.title	Synthesis and Use of Selenonic Acids as Epoxidation Catalysts and Mechanistic Investigation of the Antioxidant Drug Ebselen
dc.type	doctoral thesis
thesis.degree.discipline	Chemistry
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.