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Insulin resistance (IR) is a common risk factor for the development of metabolic diseases, and has gradually become a hot issue for research. It was reported that excessive feeding with high fructose induced insulin resistance in both humans and rats. The aim of this study was to investigate the progression of IR and identify potential biomarkers in urine, plasma and fecal extracts of high fructose-fed rats using a (1)H NMR-based metabonomics approach. The biochemical analysis was also performed. The levels of pyruvate and lactate in the plasma of the IR model rats were reduced significantly, and the levels of citrate and α-ketoglutaric acid (α-KG) in their urine, and the levels of succinate in their feces also decreased, suggesting perturbation of energy metabolism. Decreased levels of taurine in urine and fecal extracts during the whole experiment, together with increased levels of creatine/creatinine in urine, revealed liver and kidney injuries. Decreased levels of choline-containing metabolites in urine and increased levels of betaine in urine and plasma demonstrated altered transmethylation. Changes in hippurate, acetate, propionate and n-butyrate levels suggested disturbance of the intestinal flora in the IR rats. This study indicated that (1)H NMR-based metabonomics can provide biochemical information on the progression of IR and offers a non-invasive means for the discovery of potential biomarkers.

The aim of the paper is to describe a new synthesis route to obtain synthetic optically active clausenamidone and neoclausenamidone and then use high‐performance liquid chromatography (HPLC) to determine the optical purities of these isomers. In the process, we investigated the different chromatographic conditions so as to provide the best separation method. At the same time, a thermodynamic study and molecular simulations were also carried out to validate the experimental results; a brief probe into the separation mechanism was also performed. Two chiral stationary phases (CSPs) were compared with separate the enantiomers. Elution was conducted in the organic mode with n‐hexane and iso‐propanol (IPA) (80/20 v/v) as the mobile phases; the enantiomeric excess (ee) values of the synthetic R‐clausenamidone and S‐clausenamidone and R‐neoclausenamidone and S‐ neoclausenamidone were higher than 99.9%, and the enantiomeric ratio (er) values of these isomers were 100:0. Enantioselectivity and resolution (α and Rs, respectively) levels with values ranging from 1.03 to 1.99 and from 1.54 to 17.51, respectively, were achieved. The limits of detection and quantitation were 3.6 to 12.0 and 12.0 to 40.0 ug/mL, respectively. In addition, the thermodynamics study showed that the result of the mechanism of chiral separation was enthalpically controlled at a temperature ranging from 288.15 to 308.15 K. Furthermore, docking modeling showed that the hydrogen bonds and π‐π interactions were the major forces for chiral separation. The present chiral HPLC method will be used for the enantiomeric resolution of the clausenamidone derivatives.