Studies Toward the Total Synthesis of Biselide A

Author: 
Date created: 
2015-05-12
Identifier: 
etd9018
Keywords: 
Total synthesis
Biselide
Haterumalide
Macrolide
Natural products
Cross metathesis
Abstract: 

The use of natural products for medicinal purposes is a tradition dating back to ancient times. To this day bioactive natural products continue to inspire a large proportion of the new pharmaceuticals that are developed each year. Many natural products serve as drug leads and inspire the synthesis and development of more potent analogues. The biselides and haterumalides are two members of a class of recently described bioactive polyketide natural products that have been found in Okinawan ascidians. Many of the biselides and haterumalides exhibit anticancer activity, yet very little material is available from the natural sources. Of particular interest is biselide A, which is the only member of this class to demonstrate selective killing of human cancer cells over healthy cells. It has been proposed that C20 oxygenation in biselide A confers this selectivity and thus, derivatives with C20 oxygenation are also of pharmaceutical interest. While multiple syntheses of haterumalides have been published, biselide A has not yet been synthesized. This thesis highlights recent efforts towards a scalable total synthesis of biselide A. Three different approaches have been explored: the first incorporates a Horner-Wadsworth-Emmons reaction as a key step, and the second and third use a cross metathesis key step. While the Horner-Wadsworth-Emmons approach was ultimately unsuccessful, our successes in the cross metathesis approach should now yield access to this potentially important natural product.

Document type: 
Thesis
Rights: 
This thesis may be printed or downloaded for non-commercial research and scholarly purposes. Copyright remains with the author.
File(s): 
Supervisor(s): 
Robert Britton
Department: 
Science: Chemistry
Thesis type: 
(Thesis) M.Sc.
Statistics: