Studies towards the total synthesis of Antascomicin A.

This thesis is concerned with the studies towards the synthesis of antascomicin A, and is divided into five sections. The first part describes the discovery and the biological properties of the natural product antascomicin A. The biological properties of the structurally related immunosuppressant natural products rapamycin and FK-506 are also discussed. The. second section reviews methods to date of synthesising the masked tricarbonyl unit which is present in antascomicin A, rapamycin, and FK-506. This includes both literature material and the novel Ley group strategies. Part three outlines the retrosynthetic analysis of antascomicin A that has been developed by the Ley group. Section four details the research that has been completed to date. The routes to the Cw-C16 aldehyde and the C17-C24 vinyl iodide are described. This includes an account of the extensive investigations into the formation of the C21-C22 trans double bond. Two successful approaches to the key coupling of the Cw-C16 aldehyde with the C1rC24 vinyl iodide to form the C10-C24 allylic alcohol are detailed, and the subsequent synthesis of the protected C10-C24 fragment is described. Investigations into the synthesis of the C25-C34 fragment are also presented. The coupling of a model stannane with the novel C30-C33 tartrate derived, butane-2,3-diacetal protected aldehyde under various Lewis acid conditions is reported. Progress towards the synthesis of conduritol systems featuring studies on the ring-closing metathesis reaction is also described. Section five is a formal account of experiments and procedures.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

1999

Author dc:creator

• Barlow, Jaqueline Sandra

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/f173c2bc-80c1-43a1-bfae-fa8b78c5711d/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.11619

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/265441