Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
Chirality. 2011 Feb;23(2):93-8. doi: 10.1002/chir.20879.
Benalaxyl (BX), methyl-N-phenylacetyl-N-2,6-xylyl alaninate, is a potent acylanilide fungicide and consist of a pair of enantiomers. The stereoselective metabolism of BX was investigated in rat and rabbit microsomes in vitro. The degradation kinetics and the enantiomer fraction (EF) were determined using normal high-performance liquid chromatography with diode array detection and a cellulose-tris-(3,5-dimethylphenylcarbamate)-based chiral stationary phase (CDMPC-CSP). The t(1/2) of (-)-R-BX and (+)-S-BX in rat liver microsomes were 22.35 and 10.66 min of rac-BX and 5.42 and 4.03 of BX enantiomers. However, the t(1/2) of (-)-R-BX and (+)-S-BX in rabbit liver microsomes were 11.75 and 15.26 min of rac-BX and 5.66 and 9.63 of BX enantiomers. The consequence was consistent with the stereoselective toxicokinetics of BX in vitro. There was no chiral inversion from the (-)-R-BX to (+)-S-BX or inversion from (+)-S-BX to (-)-R-BX in both rabbit and rat microsomes. These results suggested metabolism of BX enantiomers was stereoselective in rat and rabbit liver microsomes.
苯并噻菌胺（BX），N-苯乙酰基-N-2,6-二甲苯基丙氨酸甲酯，是一种有效的酰苯胺类杀菌剂，由一对对映异构体组成。本研究采用大鼠和兔肝微粒体体外孵育方法，考察了 BX 的立体选择性代谢。采用常规高效液相色谱-二极管阵列检测法，以纤维素三-（3,5-二甲基苯基氨基甲酸酯）手性固定相（CDMPC-CSP）为分析手段，测定了 BX 对映体的降解动力学和对映体分数（EF）。在大鼠肝微粒体中，rac-BX 及其对映体（-）-R-BX 和（+）-S-BX 的 t(1/2)分别为 22.35、10.66 和 5.42 min；而在兔肝微粒体中，rac-BX 及其对映体（-）-R-BX 和（+）-S-BX 的 t(1/2)分别为 11.75、15.26 和 5.66 min。结果与 BX 在体外的立体选择性毒代动力学一致。在兔和大鼠肝微粒体中，（-）-R-BX 没有转化为（+）-S-BX，（+）-S-BX 也没有转化为（-）-R-BX。这些结果表明 BX 对映体在大鼠和兔肝微粒体中的代谢具有立体选择性。
