Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase
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....
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2020
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| Online Access: | https://eprints.nottingham.ac.uk/63797/ |
| _version_ | 1848800058048249856 |
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| author | Eastman, H |
| author_facet | Eastman, H |
| author_sort | Eastman, H |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 |
| first_indexed | 2025-11-14T20:45:31Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-63797 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:45:31Z |
| publishDate | 2020 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-637972025-02-28T15:07:06Z https://eprints.nottingham.ac.uk/63797/ Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase Eastman, H 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 2020-12-31 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/63797/1/Final%20Thesis%20Harry%20Eastman%283%29.pdf 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. Chemistry Jerantinine alkaloids Synthesis Biocatalytic |
| spellingShingle | Chemistry Jerantinine alkaloids Synthesis Biocatalytic Eastman, H Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase |
| title | Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase |
| title_full | Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase |
| title_fullStr | Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase |
| title_full_unstemmed | Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase |
| title_short | Total Synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - Disubstituted tetrahydropyrans using an alcohol dehydrogenase |
| title_sort | total synthesis of jerantinine alkaloids and a biocatalytic synthesis of 2,6 - disubstituted tetrahydropyrans using an alcohol dehydrogenase |
| topic | Chemistry Jerantinine alkaloids Synthesis Biocatalytic |
| url | https://eprints.nottingham.ac.uk/63797/ |