This program is directed towards an enantioselective total synthesis of brevetoxin B (1) a newly discovered marine toxin, responsible for catastrophic poisoning of marine life. The proposed synthesis relies heavily on new synthetic technology and particularly on three key operations, namely, a. stereoselective construction of allylic functions, b. asymmetric epoxidation of these functions and c. ringselective cyclizations using alkoxyepoxide functionalities to form the O-heterocycles of the molecule. The various intermediates synthesized and the final products could be useful as biolgoical tools for biosynthetic, neurological, toxicological/antitoxicological studies with potential for eliminating large scale poisoning of seafood and other marine resources consumed by humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031398-03
Application #
3279384
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1983-01-01
Project End
1985-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Nicolaou, K C (2009) Inspirations, discoveries, and future perspectives in total synthesis. J Org Chem 74:951-72
Gawley, R E; Rein, K S; Jeglitsch, G et al. (1995) The relationship of brevetoxin 'length' and A-ring functionality to binding and activity in neuronal sodium channels. Chem Biol 2:533-41
Erickson, A H (1989) Biosynthesis of lysosomal endopeptidases. J Cell Biochem 40:31-41