Chiral analysis and semi-preparative separation of metconazole stereoisomers by supercritical fluid chromatography and cytotoxicity assessment in vitro.

Abstract

Metconazole is one of the widely-used chiral triazole fungicides in controlling wheat leaf rust, powdery mildew, Fusarium head blight with high efficacy, and so forth. In the current work, the effects of chiral stationary phases, alcoholic modifiers, and column temperature on the chiral separation of metconazole were discussed in detail. Amylose tris(3,5-dimethylphenylcarbamate)-coated chiral stationary phase exhibited much stronger chiral recognition ability toward metconazole stereoisomers in the CO2 /ethanol mixture as compared to the others. Then, a two-step semi-preparative separation of metconazole was performed through supercritical fluid chromatography and high-performance liquid chromatography, and the enantiomeric excess values of four stereoisomers were achieved over 98%. Moreover, the enantioselective cytotoxicity of cis-metconazole against HepG2 cells has been investigated, and the order of the cell proliferation toxicity against HepG2 cells was (1R, 5S)-metconazole>(1S, 5R)-metconazole>the mixture. Briefly, this study would provide valuable information in the preparative separation of optically pure metconazole products through chromatographic techniques and their environmental risk assessment.