Nature：成功人工合成一种细胞毒素

海鲜中毒可由若干种毒素引起，其中包括chlorosulpholipids。因其结构上及立体化学上的复杂性，也因为它们生物反应的机制仍然不清楚，这些分子尤为让人感兴趣。这些天然产物数量有限，这使得对它们进行深度生物化学研究很困难。
本期Nature报告了一种chlorosulpholipid细胞毒素的首次完全合成，从而为全面药理定性及就其对人类健康的风险进行正确评估开辟了途径。合成工作证实了人们为chlorosulpholipids所提出的结构，而初步的发现之一是该分子内多氯烃所具有的出乎意料的反应活性。
Nature 457, 573-576 (29 January 2009) | doi:10.1038/nature07734

Total synthesis of a chlorosulpholipid cytotoxin associated with seafood poisoning

Christian Nilewski1, Roger W. Geisser1 & Erick M. Carreira1

1 Laboratorium für Organische Chemie, ETH Zürich, CH-8093 Zürich, Switzerland
Each year, there are many cases of seafood poisoning in humans worldwide1. Among the various toxins isolated that contribute to these poisonings2, 3, the chlorosulpholipids are particularly intriguing because of their structural and stereochemical complexity4, 5, 6, 7, 8, 9, 10, 11, 12. The mechanism of biological activity remains unknown and, although chlorosulpholipids are associated with membranes in the organisms from which they are isolated, little is understood about their role within biological membranes. The lack of availability of the natural products has impaired more in-depth biochemical studies. So far, none of the chlorosulpholipids have been obtained from total synthesis, and efficient routes to their synthesis would be desirable for the preparation of material for pharmacological characterization and proper evaluation of the risk to human health. Despite the notable advances in the science of organic synthesis, reliable methods for stereoselective construction of polychlorinated acyclic substrates are lacking, although some preliminary investigations have appeared13, 14, 15. Here we report the synthesis of a chlorosulpholipid cytotoxin, leading to confirmation of the proposed structure and the discovery of unanticipated reactivity of polychlorinated hydrocarbons. The concise synthetic approach should enable the preparation of material in sufficient quantities to facilitate biological studies.