The welwitindolinone class of natural products were recently isolated from cyano-bacterial sources and show promise for the treatment of multi-drug resistant tumor cells. Some members of this class of compounds exhibit chemoresistance reversing activities below toxic doses. Other members, including welwistatin, are cytotoxic agents which act by inhibiting microtuble formation in both drug sensitive and multi- drug resistance tumor cells. This proposal outlines an enantioselective synthesis of welwistatin as a representative member of this class of compounds exhibit chemoresistance reversing activities below toxic doses. Other members, including welwistatin, are cytotoxic agents which act by inhibiting microtuble formation in both drug sensitive and multi- drug resistance tumor cells. This proposal outlines an enantioselective synthesis of welwistatin as a representative member of this class of compounds. The key step in the synthesis is a novel Lewis acid catalyzed enamine cyclization-Pinacol rearrangement which simultaneously assembles the bicyclic core and installs the critical quaternary bridgehead center.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA084772-02
Application #
6377751
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lohrey, Nancy
Project Start
2001-03-03
Project End
Budget Start
2001-03-03
Budget End
2002-03-02
Support Year
2
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
Harvard University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138