? A novel methodology for the synthesis of important bicyclic and polycyclic ring systems is proposed, along with its application to a natural product synthesis. The method includes a vinylogous Morita-Baylis-Hillman reaction and subsequent aldol condensation, performed in a single step and using a single catalyst. The significance of this method will then be demonstrated in the synthesis of the pentacyclic triterpene portion of QS-21, a potent cancer and HIV vaccine adjuvant. The synthetic strategy involves the proposed method in an elegant cyclization step, which should generate three of the five ring systems in a single step. While time constraints of a two-year postdoctoral appointment will not allow synthesis of the entirety of QS-21 by the applicant, it is anticipated that the sponsor's group may ultimately complete the total synthesis of this molecule using their glycoside methodology. In addition to contributing to the limited literature on the synthesis of the structurally complex pentacyclic triterpenes, a total synthesis of this important molecule would provide sufficient material necessary for extensive biological investigations. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM073325-01
Application #
6881940
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Marino, Pamela
Project Start
2005-01-01
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
1
Fiscal Year
2005
Total Cost
$42,068
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109