Chemoenzymatic routes to enantiopure hydroxytetrahydrofurans: muscarine and its analogues

Beecher, Denis

Restricted to everyone for five years. Restriction lift date: 2021-09-07T09:07:52Z

Chemoenzymatic routes to enantiopure hydroxytetrahydrofurans: muscarine and its analogues

dc.check.date	2021-09-07T09:07:52Z
dc.check.embargoformat	Both hard copy thesis and e-thesis	en
dc.check.entireThesis	Entire Thesis Restricted
dc.check.info	Restricted to everyone for five years	en
dc.check.opt-out	Not applicable	en
dc.check.reason	Releasing this thesis would cause substantial prejudice to the commercial interests of University College Cork	en
dc.contributor.advisor	Maguire, Anita R.	en
dc.contributor.advisor	Mccarthy, Daniel G.	en
dc.contributor.author	Beecher, Denis
dc.contributor.funder	Irish Research Council	en
dc.contributor.funder	University College Cork	en
dc.date.accessioned	2016-09-08T09:07:52Z
dc.date.issued	2015
dc.date.submitted	2015
dc.description.abstract	Muscarine was identified as an active principle of the poisonous mushroom Amanita muscaria over 170 years ago and has been identified as an agonist of acetylcholine. The synthesis of all stereoisomers of muscarine have been accomplished at this stage by chemical methods and the biological activity of these compounds tested. A number of synthetic routes to enantiomerically pure muscarine and its analogues have been published. In this work, we are focussed on the use of a novel biotransformation strategy to access these compounds. Asymmetric synthesis involves targeting a synthetic pathway leading to one enantiomer of a compound and biocatalysis is one strategy used in asymmetric synthesis. Chapter 1 consists of a review of the relevant literature pertaining to the synthesis and stereoselective transformations of 3-hydroxytetrahydrofuranss. A review of synthetic routes to these compounds is presented, with a particular focus on routes to the natural product muscarine and its analogues. Chapter 2 discusses the preparative routes to the 3-hydroxytetrahydrofurans via 3(2H)- furanones. Steps amongst which include Rh(II) mediate cyclisation and kinetic resolution via baker’s yeast mediated carbonyl reduction, resulting in enantioenriched 3- hydroxytetrahydrofuran derivatives. Finally, application of this methodology to the preparation of all four enantiomers of an analogue of desmethylmuscarine and the synthesis of epimuscarine is described. Chapter 3 consists of a detailed experimental section outlining the synthetic procedures employed.	en
dc.description.sponsorship	Irish Research Council (EMBARK initiative RS.2005.7)	en
dc.description.status	Not peer reviewed	en
dc.description.version	Accepted Version
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Beecher, D. 2015. Chemoenzymatic routes to enantiopure hydroxytetrahydrofurans: muscarine and its analogues. PhD Thesis, University College Cork.	en
dc.identifier.endpage	278	en
dc.identifier.uri	https://hdl.handle.net/10468/3071
dc.language.iso	en	en
dc.publisher	University College Cork	en
dc.rights	© 2015, Denis Beecher.	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	en
dc.subject	3(2H)-furanone	en
dc.subject	3-hydroxytetrahydrofuran	en
dc.subject	Bakers' yeast	en
dc.subject	Muscarine	en
dc.subject	Desmethylmuscarine	en
dc.subject	Diazo	en
dc.thesis.opt-out	false
dc.title	Chemoenzymatic routes to enantiopure hydroxytetrahydrofurans: muscarine and its analogues	en
dc.type	Doctoral thesis	en
dc.type.qualificationlevel	Doctoral	en
dc.type.qualificationname	PhD (Science)	en
ucc.workflow.supervisor	a.maguire@ucc.ie