The specific aim of this proposal is to probe the biosynthesis of novel prenylated alkaloids containing a [2.2.2] bridged diketopiperazine ring system. Of particular interest to this program are avrainvillamide, a cytotoxic marine alkaloid, and stephacidin B, a potent inhibitor of testosterone-dependent prostate LNCaP cells. During the proposal period, an effort will be made to develop a complete biosynthetic picture of each natural product. Considering that stephacidin B appears to be a dimer of avrainvillamide, a special emphasis will be placed upon exploring the nature of the dimedzation and its role during the biosynthesis of stephacidin B. In order to provide validity to our biosynthetic claims, several synthetic and radiolabelled experiments that will be conducted are described. In addition to the biosynthetic investigation, a biomimetically patterned total synthesis of stephacidin B will be carried out in order to further explore the medicinal properties of this complex 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 #
5F32GM072296-02
Application #
6931129
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Okita, Richard T
Project Start
2004-07-15
Project End
2007-01-12
Budget Start
2005-07-15
Budget End
2007-01-12
Support Year
2
Fiscal Year
2005
Total Cost
$43,976
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Grubbs, Alan W; Artman 3rd, Gerald D; Tsukamoto, Sachiko et al. (2007) A concise total synthesis of the notoamides C and D. Angew Chem Int Ed Engl 46:2257-61