A research group at The Scripps Research Institute headed by K.C. Nicolaou, Ph.D., chairman of the Chemistry Department and the Darlene Shiley Professor in that department, has achieved the first total synthesis of brevetoxin B, a powerful and complex biotoxin associated with "red tide" catastrophies. Members
of this family of biotoxins have been responsible for environmental and economic damage, massive fish kills and human poisonings worldwide."Red tide" commonly refers to the vast blooms of certain single-cell alge, so-named because of the dense growth of pigmented algae, which are the base of the marine food chain. Only a few of the thousands of species of algae are associated with toxin production, but these "red tides" can be catastrophic: threatening humans via poisonous seafood consumption; damaging a wide array of marine life, including fish, shellfish, dolphins and whales; and causing environmental pollution.
Nicolaou believes that the developed synthetic route to brevetoxin will almost certainly lead to a better understanding of the "red tide" phenomena, perhaps even to better ways of warning against them, controlling and even eradicating them. Recognizing the peril associated with "red tides," biologists and chemists have worked for years to isolate and identify a number of marine biotoxins and their producing phytoplankton species.
"The molecular structure of brevetoxin B is architecturally elegant and extremely complex," Nicolaou reports. "Ever since its discovery in 1981, organic chemists have viewed its synthesis as a hopelessly remote possibility." Nicolaou notes that the research team's work, reported recently in the Journal of the American Chemical Society, may ultimately impact diverse scientific disciplines and promises to aid in the development of new diagnostics and therapeutics, as well as having already led to the discovery of new methods in synthetic technology.
Among the next goals of the research may be to devise a diagnostic test to distinguish between poisonous and nonpoisonous fish and to develop affective therapy for people poisoned during the outbreaks.
In addition to Nicolaou, postdoctoral fellows P.P.J.T. Rutjes, E.A. Theodorakis, J. Tiebes, M. Sato and E. Untersteller were members of the final scientific team; 25 graduate students and postdoctoral fellows at the University of Pennsylvania and the Universisty of California, San Diego, also contributed to the research over the 12-year period of the project. The research was financially supported by the National Institutes of Health, The Scripps Research Institute and fellowships from the Netherlands Organization for Scientific Research (Netherlands), the DeutscheForschungsgemeinschaft (Germany), Unitika Ltd. (Japan) and Rhone Poulenc S.A. (France).