The total synthesis of biologically active natural products drives the development of new chemistry and generates lead compounds for medical research. The object of this proposal is the asymmetric total synthesis of tubelactomicin A and kijanolide, both biologically active natural products. The kijanolide synthesis will couple a known upper half fragment with a novel dioxinone containing diene via a Suzuki cross-coupling reaction. A tandem IMDA/ketene sequence should furnish both the decalin core and the requisite keto ester moiety in a single step. Installation of the last structural element of the molecule, the spirotetronate moiety, will employ a Dieckmann cyclization of the keto ester. Deprotection and a functional group transformation will afford kijanolide. Tubelactomicin A has biological activity suggesting potential as a lead for antitubercular drugs. A cross-coupling reaction of two chiral halves of the molecule will precede the cycloaddition reaction. The salient part of this synthesis is based upon the use of a steric directing group to achieve a highly stereoselective IMDA reaction to give the trans-fused decalin portion of the molecule. Macrolactonization will afford the natural product.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM068298-02
Application #
6767821
Study Section
Special Emphasis Panel (ZRG1-F04 (20))
Program Officer
Lograsso, Philip
Project Start
2003-05-01
Project End
2005-03-31
Budget Start
2004-05-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$39,853
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