Synthesis of nucleotides from low oxidation state phosphorus starting materials
Publication Date
July 19, 2019
Creator
Rowles, Rebecca Alexandra
Abstract
In this thesis we present our work towards the synthesis of oligonucleotides from a H-Phosphinate source instead of the current synthetic methods which use PCl3 derived compounds.
Chapter 1 introduces oligonucleotides, their use in the pharmaceutical industry and the previous synthetic routes used to obtain these.
Chapter 2 documents our synthetic effort for the synthesis of H-phosphinates in part 1, and the synthesis of H-phosphonates in part 2. We use both previously established esterification and coupling reagents, as well as metal catalysis for these transformations. We find that H-phosphinic acid is to acidic for use with nucleosides and develop conditions for the synthesis of H-phosphinates and H-phosphonates from phosphinic acid salts and phosphonic acid salts. We then go on to discuss our work towards the synthesis of dinucleotides from H-phosphonates, containing the H-phosphonate, phosphonate and phosphorothioate linker. We then detail our attempts to develop this reaction using solid supported reagents with the view to performing this reaction “in-flow”.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Subjects (LC)
Associated Schools / Departments
School of Chemistry
eprints ID
56760
UoN Repository URI
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Name
Rebecca A Rowles 4238211.pdf
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Full-text
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1.83 MB
Format
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