Stereoselective Degradation of Chiral Fungicide Myclobutanil in Rat Liver Microsomes†. Issue 1 (19th November 2013)

• Record Type: Journal Article
• Authors: Yan, Jin; Zhang, Ping; Wang, Xinru; Wang, Yao; Zhou, Zhiqiang; Zhu, Wentao
• Is Part Of: Chirality. Volume 26:Issue 1(2014:Jan.)
• Page Start: 51
• Page End: 55
• Publication Date: 2013-11-19
• Subjects: Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22265
• Languages: English
• ISSNs: 0899-0042

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Myclobutanil, (RS)‐2‐(4‐chlorophenyl)‐2‐(1H‐1, 2, 4‐triazol‐1‐ylmethyl)hexanenitrile is a broad‐spectrum systemic triazole fungicide which consists of a pair of enantiomers. The <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">stereoselective</named-content> degradation of myclobutanil was investigated in rat liver microsomes. The concentrations of myclobutanil enantiomers were determined by high‐performance <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">liquid chromatography</named-content> (HPLC) with a cellulose‐tris‐(3, 5‐dimethyl‐phenylcarbamate)‐based chiral stationary phase (CDMPC‐CSP) under <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">reversed phase</named-content> condition. The t<sub>1/2</sub> of (+)‐myclobutanil is 8.49 min, while the t<sub>1/2</sub> of (–)‐myclobutanil is 96.27 min. Such consequences clearly indicated that the degradation of myclobutanil in rat liver microsomes was <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">stereoselective</named-content> and the degradation rate of (+)‐myclobutanil was much faster than (–)‐myclobutanil. In addition, significant differences between two enantiomers were also observed in enzyme kinetic parameters. The V<sub>max</sub> of (+)‐myclobutanil was about 4‐fold of (–)‐myclobutanil and the CL<sub>int</sub> of (+)‐myclobutanil was three times as much as (–)‐myclobutanil after incubation in rat liver microsomes. Corresponding consequences may shed light on the environmental and ecological <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">risk assessment</named-content> for myclobutanil and may improve human health. <italic>Chirality 26:51–55, 2013.</italic> © 2013 Wiley Periodicals, Inc.</p> </abstract>