Zhang, Xiangyu;
(2019)
Towards Schizozygine Type Alkaloids: Total Synthesis of (+)-Vallesamidine and (+)-Strempeliopine.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
As a classic and powerful tool for carbon-carbon bond formation, the nitro-Mannich reaction has shown its versatility in drugs and natural products syntheses. The 1,2-diamine structure, a reduced moiety from nitro-Mannich adduct, is widely present in naturally occurring alkaloids and this feature suggested the potential application of nitro-mannich reaction in such alkaloids synthesis. This thesis showcases the nitro-Mannich reaction as a key strategic reaction through studies towards the total synthesis of 1,2-diamine contained alkaloids, schizozygine, vallesamidine and strempeliopine (Chapter 1 and 2). Initial studies on the schizozygine molecule (Chapter 3) generated a diastereoselective nitro-Mannich reaction on -branched nitroalkanes to synthesise complex -nitroamines with three contigurous chiral centres and syn,anti stereochemistry. This reaction was followed by a reductive cyclisation to achieve the functionalised piperidine ring C. Although the subsequent manipulation towards advanced shcizozygine intermediate was unsuccessful, the nitro-Mannich/reductive cyclisation sequence provided methodology for highly functionalised piperidine ring synthesis. A second generation route using nitro-Mannich reaction was accompanied by other nitro group chemistry, Michael addition, Tsuji-Trost allylation and nitro group reduction/C-N coupling reaction, to realise the quick and concise preparation of an A/B/C ring intermediate. An unusual and novel [1,4]-hydride tansfer/Mannich type cyclisation was carried out to build the ring E. The resulting A/B/C/E ring intermediate was used divergently to complete the total synthesis of (+)-vallesamidine (Chapter 4) and (+)-14,15-dehydrostrempeliopine (Chapter 5) as well as three other unnatural analogues. These natural and unnatural products could be candidates for drug discovery research and the route would be applicale for the synthesis of schizozygine and related molecules.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Towards Schizozygine Type Alkaloids: Total Synthesis of (+)-Vallesamidine and (+)-Strempeliopine |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10082025 |
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