The research described in this proposal will provide access to tetrodotoxin, a potent neurotoxin widely used in pharmacological studies as a probe for sodium channels. This highly complex molecule will be assembled in optically pure form in a concise manner using a novel synthetic strategy. Furthermore, the proposed synthetic route is flexible enough to permit preparation of natural congeners of tetrodotoxin as well as its nonnatural analogs. The structure-activity relationship study of these derivatives, which cannot be accessed by chemical modification of tetrodotoxin itself, will make possible a better understanding of the structure and the mechanism of action of the sodium channel.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS041726-02
Application #
6613711
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Stewart, Randall
Project Start
2002-05-29
Project End
Budget Start
2002-05-29
Budget End
2003-05-28
Support Year
2
Fiscal Year
2002
Total Cost
$38,320
Indirect Cost
Name
Columbia University (N.Y.)
Department
Chemistry
Type
Other Domestic Higher Education
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Birman, Vladimir B; Danishefsky, Samuel J (2002) The total synthesis of (+/-)-merrilactone A. J Am Chem Soc 124:2080-1