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A novel approach towards the stereoselective synthesis of inositols and its application in the synthesis of biologically important molecules
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dc.contributor.advisor | Smith, Terry K. | |
dc.contributor.advisor | Florence, Gordon John | |
dc.contributor.author | Sayer, Lloyd | |
dc.coverage.spatial | 180 | en_US |
dc.date.accessioned | 2018-07-23T15:15:11Z | |
dc.date.available | 2018-07-23T15:15:11Z | |
dc.date.issued | 2016-06-22 | |
dc.identifier.uri | https://hdl.handle.net/10023/15658 | |
dc.description.abstract | Myo-inositol is ubiquitous in nature and is found at the structural core of a diverse range of biologically important derivatives, including phosphatidylinositols, inositol phosphates and mycothiol. The synthesis of myo-inositol derivatives is notoriously difficult due to the need to control both regio- and enantioselectivity. As a result, synthetic routes to derivatives of this type are often lengthy and low yielding. The first biosynthetic step in the production of all myo-inositol metabolites is the isomerisation of D-glucose 6- phosphate to L-myo-inositol 1-phosphate as mediated by L-myo-inositol 1-phosphate synthase (INO1). For the protozoan parasite Trypanosoma brucei, INO1 is essential for survival and its version of the enzyme (TbINO1) has a high turnover. This makes TbINO1 an attractive candidate for the biocatalytic production of L-myo-inositol 1- phosphate, and a potential starting point for drastically shortened syntheses of important myo-inositol derivatives. The production of L-myo-inositol 1-phosphate by TbINO1 has been optimised to achieve complete conversion in reaction conditions that facilitate product isolation. Due to problems with an in-batch process, the TbINO1 enzyme was immobilised and the process was transferred to a flow system. This has allowed for production of significant quantities of L-myo-inositol 1-phosphate with a high level of purity. L-myo-inositol 1- phosphate obtained from the flow system has been used to prepare mycothiol glycosylation acceptor, 1,2,4,5,6-penta-O-acetyl-D-myo-inositol, in a concise synthesis with a greatly improved yield over the literature. | en_US |
dc.language.iso | en | en_US |
dc.publisher | University of St Andrews | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Biocatalysis | en_US |
dc.subject | Inositol | en_US |
dc.subject | Mycothiol | en_US |
dc.subject | L-myo-inositol 1-phosphate synthase | en_US |
dc.subject | INO1 | en_US |
dc.subject | Enantioselective | en_US |
dc.subject | Flow chemistry | en_US |
dc.subject | Trypanosoma brucei | en_US |
dc.subject | L-myo-inositol 1-phosphate | en_US |
dc.subject.lcc | QP772.I5S2 | |
dc.subject.lcsh | Inositol | en |
dc.subject.lcsh | Biocatalysis | en |
dc.subject.lcsh | Flow chemistry | en |
dc.subject.lcsh | Trypanosoma brucei | en |
dc.title | A novel approach towards the stereoselective synthesis of inositols and its application in the synthesis of biologically important molecules | en_US |
dc.type | Thesis | en_US |
dc.contributor.sponsor | Biotechnology and Biological Sciences Research Council (BBSRC) | en_US |
dc.type.qualificationlevel | Doctoral | en_US |
dc.type.qualificationname | PhD Doctor of Philosophy | en_US |
dc.publisher.institution | The University of St Andrews | en_US |
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