A thesis submitted to the Faculty of Science, University of the Witwatersrand Johannesburg.
In fulfilment of the requirements for the Degree of Doctor of Philosophy.
March 2017 / In this PhD thesis, we report for the first time, new methodology for the synthesis of angucycline antibiotic natural products. In particular, for the synthesis of 1,8-dihydroxy-3methyltetraphene-7,12-dione, commonly known as tetrangulol. We also report on the synthesis of 1,10,12-trimethoxy-8-methylbenzo[c]phenanthridine in our quest to synthesise phenanthroviridone from an intermediate product in the synthesis of tetrangulol.
The Suzuki-Miyaura coupling reaction between 1,4,5-(trimethoxynaphthalen-2-yl)boronic acid and 2-iodo-3-methoxy-5-methylbenzaldehyde afforded intermediate, 3-methoxy-5methyl-2-(1,4,5-trimethoxynaphthalen-2-yl)benzaldehyde. Conversion of this benzaldehyde into the alkyne, 2-(2-ethynyl-6-methoxy-4-methylphenyl)-1,4,5-trimethoxynaphthalene was accomplished utilizing the Corey-Fuchs reaction. Exposure of the derived acetylene to a catalytic platinum(II)-mediated ring closure yielded the required tetracyclic aromatic product, 1,7,8,12-tetramethoxy-3-methyltetraphene which was converted into tetrangulol. Exposure of the related 3-methoxy-5-methyl-2-(1,4,5-trimethoxynaphthalen-2-yl)benzaldehyde O-phenyl oxime to microwave irradiation in an ionic liquid yielded 1,10,12-trimethoxy-8methylbenzo[c]phenanthridine, instead of the desired natural product phenanthroviridone.
We also report on the unexpected synthesis of the benzonaphthopyranone core found in other classes of angucycline antibiotics from oxygen analogs of 2-naphthylbenzyl alcohols when exposed to N-bromosuccinimide. Treatment of (2-(1,4-dimethoxynaphthalen-2yl)phenyl)methanol and related analogues with N-bromosuccinimide under an oxygen atmosphere afforded 12-methoxy-6H-dibenzo[c,h]chromen-6-one, 2-Methoxy-6Hbenzo[c]chromen-6-one and of 6H-benzo[c]chromen-6-one. An investigation into possible mechanisms for this transformation was also conducted. / LG2017
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/23521 |
| Date | January 2017 |
| Creators | Ngwira, Kennedy John Vijuviju |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | Online resource (xiv, 252 leaves), application/pdf, application/pdf, application/pdf |
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