Asymmetric synthesis of novel anthracyclinones

The synthesis of novel C9-halogenated anthracyclinones by Lewis acid promoted cyclisations of ortho-methallyl anthraquinonyl chiral dioxanes has been investigated. Tin tetrachloride-N,N-dimethylformamide promoted cyclisation of the dioxane (30) proceeded with excellent stereoselectivity to give an 82% yield of the diastereomerically pure chlorotetracycle (78). Stronger Lewis acids gave poorer selectivity and boron trifluoride etherate reacted slowly with (30) but with high selectivity to give the diastereomerically pure fluorotetracycle (91) in 58% yield. The presence of a β-methoxy group in the substrate leads to decreased stereoselectivity due to competition between chelation and non-chelation controlled pathways. Stereochemistry was assigned to the products using a combination of X-ray crystallography, conformational analysis, nuclear Overhauser enhancements and chemical degradation. Attempts were made to extend the highly selective acetal cyclisation methodology to the intramolecular reaction of the allylsilane (121), cyclisation of which was expected to provide enantioselective access to the alkene (146). The synthesis of (121) was achieved despite its instability, but attempted cyclisations with Lewis acids or fluoride ions were unsuccessful. The racemic alkene (146) was prepared by an ene cyclisation and subjected to asymmetric dihydroxylation (AD). The products from the AD reactions are of considerable biological interest and have been characterized. Their stereochemistry has been assigned by 1H nmr comparisons with the parent diphenols, which have resulted in revisions of assignments made by earlier workers.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

1995

Author dc:creator

• Rustenhoven, Job Jesse

Advisor dc:contributor.advisor

• Stew Rutledge

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/2292/1903

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/1903