The continuing saga of the marine polyether biotoxins

The unprecedented structure of the marine natural product brevetoxin B was elucidated by the research group of Nakanishi and Clardy in 1981. The ladderlike molecular architecture of this fused polyether molecule, its potent toxicity, and fascinating voltage-sensitive sodium channel based mechanism of action immediately captured the imagination of synthetic chemists. Synthetic endeavors resulted in numerous new methods and strategies for the construction of cyclic ethers, and culminated in several impressive total syntheses of this molecule and some of its equally challenging siblings. Of the marine polyethers, maitotoxin is not only the most complex and most toxic of the class, but is also the largest nonpolymeric natural product known to date. This Review begins with a brief history of the isolation of these biotoxins and highlights their biological properties and mechanism of action. Chemical syntheses are then described, with particular emphasis on new methods developed and applied to the total syntheses. The Review ends with a discussion of the, as yet unfinished, story of maitotoxin, and projects into the future of this area of research.     

The chemistry and biological function of natural marine toxins

Studies on ciguatera fish poisoning led to clarification of the absolute stereochemistry of ciguatoxin, gambierol, gambieric acids, and maitotoxin. Anisotropic NMR reagents and fluorometric chiral HPLC reagents were effectively used together with synthesis of partial structures. Structures of 16 ciguatoxin congeners were successfully elucidated by FAB/MS/MS using samples of 5 microg or less. Stereochemical assignments were also achieved on dinophysistoxin-1, pectenotoxins, yessotoxins, polycavernoside-A, azaspiracid, and prymnesins. The toxins possessed poly-cyclic-ether structures and originated from unicellular algae. Biological functions are briefly described.     

Marine huge molecules: the longest carbon chains in natural products

Marine huge polyol and polyether compounds are remarkable molecules owing to their extraordinary structures and significant biological activities. Currently, palytoxin and maitotoxin are believed to have the longest carbon chains in nature (more than 100 Å in length), except for biopolymers. The structural properties of such marine huge molecules are highlighted, especially with regard to the length and shape of their carbon chains. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 10: 000–000; 2010: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.200900030