Conformational analogs of Peloruside A

ORGN 456

Zhiming Zhao, zzhao1@nd.edu, Department of Chemistry and Biochemistry andWalther Cancer Research Center, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556 and Richard E. Taylor, taylor.61@nd.edu, Department of Chemistry & Biochemistry and Walther Cancer Research Center, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556.
Peloruside A is a cytotoxic macrolide that was isolated from a New Zealand marine sponge, Mycale hentscheli. It has potent paclitaxel-like microtubule-stabilizing activity and is highly cytotoxic. As part of our overall program to explore the therapeutic potential of polyketide natural products, we are exploring analogues of peloruside A guided by an understanding of its solution conformational preferences. As a complement to our previously reported total synthesis, we have developed an alternative expedient route to late-stage peloruside analogues which will probe the bound through systematic modification of key torsions. Our design strategy as well as recent progress will be presented.
 

Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- Rm. R05, Oral

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008