Enantiomeric separation of prothioconazole and prothioconazole‐desthio on chiral stationary phases

Abstract

Prothioconazole is a type of broad-spectrum triazole thione fungicide developed by the Bayer Company. Prothioconazole-desthio is the main metabolite of prothioconazole in the environment. In our study, enantiomeric separation of prothioconazole and prothioconazole-desthio was performed on various chiral stationary phases (CSPs) by high-performance liquid chromatography (HPLC). It was found that polysaccharide CSPs showed better ability than brushing CSPs in enantiomeric separation. The successful chiral separation of prothioconazole could be achieved on self-made Chiralcel OD, commercialized Chiralcel OJ-H and Lux Cellulose-1. Chiralpak IA, Chiralpak IB, Chiralpak IC, Chiralcel OD, Chiralpak AY-H, Chiralpak AZ-H, and Lux Cellulose-1 realized the baseline separation of prothioconazole-desthio enantiomers. Simultaneous enantiomeric separation of prothioconazole and prothioconazole-desthio was performed on Lux Cellulose-1 using acetonitrile (ACN) and water as mobile phase. In most cases, low temperature favored the separation of two compounds. The influence of the mobile phase ratio or type was deeply discussed. We obtained larger Rs and longer analysis time with a smaller proportion of isopropanol (IPA) or ethanol and more water content at the same temperature. The ratio of ACN and water had influences on the outflow orders of prothioconazole-desthio enantiomers. This work provides a new approach for chiral separation of prothioconazole and prothioconazole-desthio with a discussion of chiral separation mechanism on different CSPs.

An overview of chiral separations of pharmaceutically active substances by HPLC (2018–2020)

“…A method for the separation of α-tocopherol enantiomers was successfully developed with a Lux Cellulose-1 column [ 57 ]. Several polysaccharide-based CSPs were tested for enantiomeric separation of the antifungal agent prothioconazole and its metabolite prothioconazole-desthio, and the Lux Cellulose-1 column was rated as the best [ 58 ]. A comparative study was performed with chiral basic drugs on amylose- and cellulose phenylcarbamate-based chiral columns with a focus on substituent electron-donor and electron-acceptor effects.…”

Survey of prothioconazole sensitivity in Fusarium pseudograminearum isolates from Henan Province, China, and characterization of resistant laboratory mutants

“…Previous research has shown that prothioconazole inhibits the 14α-demethylation of lanolin, which is the precursor of sterol biosynthesis in fungi, and therefore should be considered a member of the sterol 14α-demethylation inhibitor (DMI) group of fungicides [ 6 – 8 ]. In addition to its broad-spectrum activity, prothioconazole has many other desirable characteristics including good internal absorption, long duration of activity, and low environmental impact [ 9 ]. The Fungicide Resistance Action Committee (FRAC) classifies DMI fungicides in the G1 subgroup of Sterol Biosynthesis Inhibitors (SBI) that are recommended for general use in all crops [ 10 ], and prothioconazole is widely used for the prevention and control of disease in field crops such as wheat, soybean, and rice [ 6 , 9 ].…”

“…In addition to its broad-spectrum activity, prothioconazole has many other desirable characteristics including good internal absorption, long duration of activity, and low environmental impact [ 9 ]. The Fungicide Resistance Action Committee (FRAC) classifies DMI fungicides in the G1 subgroup of Sterol Biosynthesis Inhibitors (SBI) that are recommended for general use in all crops [ 10 ], and prothioconazole is widely used for the prevention and control of disease in field crops such as wheat, soybean, and rice [ 6 , 9 ]. Indeed, studies have shown that prothioconazole provides excellent control of almost all fungal diseases, with especially high activity against wheat scab, dry blight, and powdery mildew [ 6 ], and that when applied at a rate of 200 g/hm 2 it provided equal to or better control than other commonly used fungicides such as epoxiconazole, tebuconazole and cyprodinil [ 9 , 11 ].…”

Enantioseparation and molecular modeling study of eight psychoactive drugs on a coated polysaccharide‐based chiral stationary phase

“…HPLC has been commonly applied to the separation and analysis of drug enantiomers because of its more prominent advantages of fast separation, high efficiency, good reproducibility, and easy operation [5][6][7][8][9] than other chiral separation methods such as CE [10] and supercritical fluid chromatography (SFC) [11][12][13]. To date, different chiral stationary phases (CSPs) have been developed to achieve the enantioseparation of various chiral drugs.…”