海鮮中毒可由若干種毒素引起,，其中包括chlorosulpholipids,。因其結(jié)構(gòu)上及立體化學(xué)上的復(fù)雜性,，也因為它們生物反應(yīng)的機制仍然不清楚，這些分子尤為讓人感興趣,。這些天然產(chǎn)物數(shù)量有限,，這使得對它們進行深度生物化學(xué)研究很困難。
本期Nature報告了一種chlorosulpholipid細(xì)胞毒素的首次完全合成,，從而為全面藥理定性及就其對人類健康的風(fēng)險進行正確評估開辟了途徑,。合成工作證實了人們?yōu)閏hlorosulpholipids所提出的結(jié)構(gòu)，而初步的發(fā)現(xiàn)之一是該分子內(nèi)多氯烴所具有的出乎意料的反應(yīng)活性,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
