Stereospecific alkynylation at the more hindered carbon of trisubstituted epoxides and concise syntheses of bis-THF acetogenins and analogues

Alkynyl aluminate reagents react cleanly at the tertiary position of trisubstituted epoxides in 75-80% isolated yield. The reaction is stereospecific with inversion at the substitution center. This work constitutes the first general method for the addition of a carbon nucleophile at the more congested site of a trisubstituted epoxide. The less efficient alkynyl alane reagents for the same transformation were also discussed. Bis-THF acetogenin bullatacin and analogues are each synthesized in 22 steps and 6.2% overall yield. The new synthesis takes a modular approach and features a cobalt mediated oxidative cyclization reaction, an efficient synthesis of epoxy butenolide, and a highly diastereoselective alkylation of a bis-THF aldehyde. The efficiency of the new synthetic sequence allows quick assembly of the series of compounds and the study of their structure and activity relationships (SARs) is currently underway.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor

The University of Texas at Austin

Year dc:date.issued

2006

Author dc:creator

• Zhao, Hongda

Advisor dc:contributor.advisor

• Pagenkopf, Brian L.

Statement dc:rights

• Copyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.

Language dc:language.iso

eng

Identifier

b64905238

OAI identifier oai:identifier

oai:repositories.lib.utexas.edu:2152/2659