Stereoisomeric separation and toxicity of the nematicide fosthiazate
Stereoisomeric separation and toxicity of the nematicide fosthiazate
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DOI：
10.1897/07-255r.1
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发表时间：
2007-11
影响因子：
4.1
通讯作者：
Kunde Lin;Feng Zhang;Shanshan Zhou;Weiping Liu;J. Gan;Zhiyan Pan
中科院分区：
文献类型：
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作者：
Kunde Lin;Feng Zhang;Shanshan Zhou;Weiping Liu;J. Gan;Zhiyan Pan
一些具有一个不对称中心的手性有机磷农药（OPs）的对映体拆分和毒性研究已经引起了相当大的关注，但关于具有两个不对称中心的手性有机磷农药的研究还很有限。本文研究了磷原子和碳原子上有两个不对称中心的手性OP——磷氮酸酯的立体异构体分离及其毒性。用Chiralpak®AD[淀粉酶三（3,5‐二甲基苯基氨基甲酸酯）]柱在高效液相色谱上成功分离了氟噻嗪酯的所有四种立体异构体。利用圆二色性检测器和旋光检测器进一步区分分离的异构体和对映异构体，确定第1 （pk1）和第3 （pk3）洗脱峰为一对对映异构体，第2 （pk2）和第4 （pk4）洗脱峰为另一对对映异构体。所开发的方法用于制备用于体外和体内生物测定的微量个体立体异构体。立体异构体对电鳗乙酰胆碱酯酶的抑制作用具有轻微的立体选择性，最大差异为1.4倍。然而，在异构体对大水蚤的急性毒性方面，观察到3.1倍的差异。同分异构体对D. magna的48 h毒性顺序为pk1 > pk2 > pk4 >外消旋体≈pk3。氟化膦对D. magna的立体选择性毒性表明，氟化膦的环境安全性应根据其单个异构体进行评价。
Considerable attention has been paid to the enantiomeric resolution and toxicity of some chiral organophosphorous pesticides (OPs) with one asymmetric center, but research concerning chiral OPs with two asymmetric centers is still limited. In the present study, the stereoisomeric separation and toxicity of fosthiazate, a chiral OP with two asymmetric centers on phosphorus and carbon atoms, was investigated. All four stereoisomers of fosthiazate were separated successfully with a Chiralpak® AD [amylase tris(3,5‐dimethyl‐phenyl carbamate)] column on high‐performance liquid chromatography. The resolved isomers and the pairs of enantiomers were further distinguished using a circular dichroism detector and an optical rotation detector, designating the first (pk1) and third (pk3) eluted peaks as one pair of enantiomers and the second (pk2) and fourth (pk4) peaks as the other pair. The developed method was used to prepare microquantities of individual stereoisomers that were used for in vitro and in vivo bioassays. The inhibition potencies of the stereoisomers against acetylcholinesterase of Electrophorus electricus were slightly stereoselective, with a maximum difference of 1.4‐fold among the isomers. A 3.1‐fold difference, however, was observed in the acute toxicity of isomers to Daphnia magna. The 48‐h toxicity of isomers to D. magna followed the order pk1 > pk2 > pk4 > racemate ≈ pk3. The stereoselective toxicity to D. magna found in fosthiazate suggests that the environmental safety of fosthiazate should be evaluated on the basis of its individual isomers.