Design and synthesis of de novo paclitaxel mimics

ORGN 851

Liang Sun, liasun@ic.sunysb.edu, Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 and Iwao Ojima, iojima@notes.cc.sunysb.edu, Department of Chemistry and ICB&DD, State University of New York at Stony Brook, The Chemistry Bldg, Stony Brook, NY 11794-3400.
Paclitaxel (Taxol®) currently serves as one of the most important drugs in cancer chemotherapy. Analysis of likely pharmacophore structures for paclitaxel-like microtubule-stabilizing agents suggests that the complex baccatin core could be mimicked by a structurally simpler scaffold that retains its essential features. We designed novel baccatin-free paclitaxel mimic 3 that can take the “REDOR-Taxol” conformation at the binding site in beta-tubulin. Fused 5-6-6 tricyclic ring system 2 has been synthesized from hydroxyproline derivative 1. A similar approach to the synthesis of fused 5-7-6 ring systems will also be discussed. Molecular modeling studies, synthesis and biological evaluation of these novel paclitaxel mimics will be presented.

 

Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 134, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006