This proposal describes a total synthesis of the marine fungal metabolite spiroxin A. In spite of a wide array of promising biological activity, which includes antibiotic and antitumor properties, no syntheses of spiroxins, either partial or total, have been reported. The construction of spiroxin A relies upon two key hypervalent iodine mediated ring closures to form the hexacyclic core structure. Iodine (III) will be used to induce both an oxidative spiroketalization and an intramolecular phenolic oxidative biaryl coupling. The possibility of achieving diasteroselectivity in the latter process and relaying that to an asymmetric synthesis of spiroxin a will also be explored. In addition, methodology for the synthesis of functionalized 1,4,5,8-tetrahydroxynaphthalenes via a sterically controlled, regioselective benzyne-furan cycloaddition will be developed to access intermediates necessary for the key coupling reaction. The proposed route to spiroxin A is concise and should allow for further biological screening and the elucidation of the SAR of this intriguing 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 #
5F32GM066509-02
Application #
6630430
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Marino, Pamela
Project Start
2002-08-01
Project End
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$41,108
Indirect Cost
Name
University of Pittsburgh
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213