Use this URL to cite or link to this record in EThOS: | https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.750188 |
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Title: | A novel approach towards the stereoselective synthesis of inositols and its application in the synthesis of biologically important molecules | ||||||
Author: | Sayer, Lloyd |
ISNI:
0000 0004 7234 4419
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Awarding Body: | University of St Andrews | ||||||
Current Institution: | University of St Andrews | ||||||
Date of Award: | 2016 | ||||||
Availability of Full Text: |
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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.
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Supervisor: | Smith, Terry K. ; Florence, Gordon John | Sponsor: | Biotechnology and Biological Sciences Research Council (BBSRC) | ||||
Qualification Name: | Thesis (Ph.D.) | Qualification Level: | Doctoral | ||||
EThOS ID: | uk.bl.ethos.750188 | DOI: | Not available | ||||
Keywords: | Biocatalysis ; Inositol ; Mycothiol ; L-myo-inositol 1-phosphate synthase ; INO1 ; Enantioselective ; Flow chemistry ; Trypanosoma brucei ; L-myo-inositol 1-phosphate ; QP772.I5S2 | ||||||
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