Cyanthiwigin diterpenoids are known to display antituberculosis and anticancer activity. Recently, cyanthiwigin AC was isolated, but not in sufficient quantities for pharmaceutical evaluation. This proposal outlines the asymmmmetric total synthesis of Cyanthiwigin AC. Cyanthiwigin AC serves as an excellent scaffold to explore new catalytic asymmetric methodology and to expand upon existing enantioselective reactions. New reactivity will be explored through the use of an asymmetric Diels-Alder reaction with a hydrazine- or diazene-substituted diene. The resulting Diels-Alder adduct can then be used to transfer chirality and enables rapid access to new substitution patterns. The key step of the synthesis is a palladium mediated Heck cascade to diastereoselectively set a spiro-ring quaternary center and to set a 5,6 cis fused skeleton. The stereo selective and convergent route will provide an efficient synthesis of cyanthiwigin AC as well as access to potentially bioactive synthetic analogs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM072230-01
Application #
6837416
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Okita, Richard T
Project Start
2004-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
1
Fiscal Year
2004
Total Cost
$41,068
Indirect Cost
Name
Princeton University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Xie, Hao; Sammis, Glenn M; Flamme, Eric M et al. (2011) The catalytic asymmetric Diels-Alder reactions and post-cycloaddition reductive transpositions of 1-hydrazinodienes. Chemistry 17:11131-4
Sammis, Glenn M; Flamme, Eric M; Xie, Hao et al. (2005) Design, synthesis, and reactivity of 1-hydrazinodienes for use in organic synthesis. J Am Chem Soc 127:8612-3