Nicolaou K C, Frederick Michael O, Aversa Robert J
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Angew Chem Int Ed Engl. 2008;47(38):7182-225. doi: 10.1002/anie.200801696.
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.
1981年，中西和克拉迪的研究小组阐明了海洋天然产物短裸甲藻毒素B前所未有的结构。这种稠合聚醚分子的阶梯状分子结构、其强大的毒性以及基于电压敏感钠通道的迷人作用机制，立即激发了合成化学家的想象力。合成研究产生了许多构建环醚的新方法和策略，并最终实现了该分子及其一些同样具有挑战性的类似物的多次令人印象深刻的全合成。在海洋聚醚中， maitotoxin不仅是该类中最复杂、毒性最大的，也是迄今为止已知的最大的非聚合天然产物。本综述首先简要介绍了这些生物毒素的分离历史，并重点介绍了它们的生物学特性和作用机制。然后描述了化学合成，特别强调了开发并应用于全合成的新方法。综述最后讨论了maitotoxin尚未完成的故事，并展望了该研究领域的未来。
