Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase

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Eastman, H (2020) Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase. PhD thesis, University of Nottingham.

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Abstract

This thesis is comprised of two sections; The first is a semi synthesis of the cytotoxic natural product jerantinine A. Starting from the natural product tabersonine, isolated from Voacanga africana, which contains the 3 stereocenters present in jerantinine alkaloids set in the correct conformation. The reaction conditions were optimised and produced jerantinine A from tabersonine in a 16% yield over 7 steps. Following this, the biological activity was evaluated using MCF-7 Cancer cell lines, a clonogenic assay, cell cycle analysis and a tubulin polymerisation assay. These results concluded that jerantinine A was a tubulin destabilising agent and were visualised using confocal microscopy.

The second section is using alcohol dehydrogenases in the formation of disubstituted tetrahydropyrans. The biocatalytic strategy of the synthesis of 2-6, disubstituted tetrahydropyrans was achieved using an alcohol dehydrogenase triggered intramolecular oxa-Michael reaction from prochiral ketoenone starting materials. These were produced in good yields with up to >99% e.e. and 12:1 d.r.. This methodology was then used in the synthesis of an analogue of the natural product brocaketone A in a 26% yield over the synthesis. 2,5-Disubstituted tetrahydrofurans were also produced using this methodology but were produced in poor d.r

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: O'Reilly, Elaine
Moses, John E.
Keywords: Chemistry, Jerantinine alkaloids, Synthesis, Biocatalytic
Subjects: Q Science > QD Chemistry
Faculties/Schools: UK Campuses > Faculty of Science > School of Chemistry
Item ID: 63797
Depositing User: Eastman, Harry
Date Deposited: 31 Dec 2020 04:40
Last Modified: 31 Dec 2022 04:30
URI: https://eprints.nottingham.ac.uk/id/eprint/63797

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