This grant application describes a program directed towards the completion of the total synthesis of the two marine toxins, brevetoxin B (1) and brevetoxin A (2). Both compounds are potent neurotoxins associated with the 'red tide' catastrophes. Their total syntheses are expected to render them available for further biological investigations and provide the opportunity for invention of new reactions and synthetic strategies. Important biological data are expected through evaluation of synthetic fragments of these compounds which may increase our knowledge in neurobiology and drug design. The significance of this work lies in chemical synthesis, and protection of the marine environment and seafood resources, as well as general biomedical research.
| 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 |
