The highly functionalized diterpene bielschowskysin was isolated in early 2004 from the gorgonian coral Pseudopterogorgia kallos and is reported to exhibit strong and specific in vitro cytotoxicity in the NCI's antitumor screen as well as potent antimalarial activity. Structurally, the tricyclo[9,3,0,0]tetradecane skeleton of bielschowskysin represents a unique diterpene architecture. The unprecedented structure of bielschowskysin combined with the potent anticancer and antimalarial activity makes this diterpene a highly attractive target for chemical synthesis. Highlights of the synthetic strategy include construction the tricyclic core ring system through the use of a cyclic silyl enol ether in an intramolecular photochemical [2+2] cycloaddition, and an intramolecular Nozaki-Hiyama-Kishi cyclization to construct the nine-membered ring of bielschowskysin. Successful total synthesis of bielschowskysin will establish the absolute configuration, provide additional material for biological testing, and allow access to analogs and intermediates, not readily available from the natural material, to evaluate the structure activity relationship of this fascinating bioactive 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 #
1F32GM075687-01
Application #
6999898
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Marino, Pamela
Project Start
2006-01-23
Project End
2007-01-22
Budget Start
2006-01-23
Budget End
2007-01-22
Support Year
1
Fiscal Year
2005
Total Cost
$42,068
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