Gill, Daniel (2020). New methods towards the synthesis, characterisation and analysis of small molecule glycomimetics. University of Birmingham. Ph.D.
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Gill2020PhD.pdf
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Abstract
This thesis is made up of five individual chapters and contains the collective works of three separate investigations.
Chapter 1 discusses the current biology and chemistry associated with the bio-macromolecules: heparin and heparan sulfate. It provides the reader with a detailed knowledge of the two molecules, their differences, similarities, biological activity and efforts taken towards their synthesis.
This leads directly into Chapter 2, which introduces heparin and heparan sulfate glycomimetics as novel drug targets, and discusses cases from the current literature. The end of Chapter 2 lists the aims set out by this investigation, justifications of those aims and the problems encountered early on in the synthesis and characterisation of target molecules intended for a study.
Chapter 3 describes a chiral high performance liquid chromatography investigation into the effects of sterics, and double diastereodifferentiation, in the Sharpless asymmetric dihydroxylation of alkenes. This work highlights how pre-existing point chirality from a distal stereocenter influences asymmetric induction and the overall enantioselectivity in the reaction, providing evidence towards a correct model of alkene-ligand binding.
Chapter 4 discusses the design and method development for the reagent Bu3N•SO3, which is capable of synthesising lipophilic organosulfates in high yield. This methodology was applied to sulfation of simple and complex alcohols (and amines), including hormones, natural products, amino acids and biologically relevant targets.
Chapter 5 draws from the work discussed in Chapters 3 and 4, and details the synthesis of a small library of heparan sulfate glycomimetics that were computationally docked into a protein’s active site, with a selection of compounds tested for biological activity.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges (former) > College of Medical & Dental Sciences | |||||||||
| School or Department: | School of Pharmacy | |||||||||
| Funders: | Other | |||||||||
| Subjects: | Q Science > QD Chemistry | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/10332 |
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