New enantioselective liquid chromatography method development and validation of dipeptidyl peptidase IV inhibitors using a macrocyclic glycopeptide (vancomycin) chiral stationary phase under polar ionic mode condition.

The direct separation of dipeptidyl peptidase IV (DPP-4) inhibitors such as Sitagliptin (STG), Linagliptin (LIG), and Saxagliptin (SAG) enantiomers in normal phase conditions have been achieved on immobilized polysaccharide-based chiral stationary phases (CSPs), as well as on the macrocyclic glycopeptide vancomycin chiral stationary phase (Chirobiotic V2) under polar ionic mode. The enantiomers of these targets could be separated completely (resolution factor Rs > 2) using the Chirobiotic V2 column in polar ionic mode with the mobile phase (MeOH/AcOH/TEA 100/0.3/0.1 v/v/v) in an isocratic elution at 1.0 ml min-1 . The effect of the mobile phase composition on separation, including buffer salts, acid-base modifiers, and analyte structures, was evaluated. The developed technique was validated in the polar ionic mode according to the International Conference on Harmonization (ICH) Q2R1 guidelines in terms of accuracy, precision, selectivity, linearity, limit of detection (LOD), and limit of quantification (LOQ). The calibration curve was linear in a concentration range from LOQ to 3.75 µg/ml. The LOD and LOQ of STG, LIG, and SAG were 0.15 and 0.45, 0.15 and 0.50, 0.16 and 0.50, respectively. The proposed method is said to be selective, accurate, and precise. Finally, the validated method was used successfully for the quantitative determination of DPP-4 enantiomers in pharmaceutical analytes.

Copper-Promoted One-Pot Approach: Synthesis of Benzimidazoles.

A facile, one-pot, and proficient method was developed for the production of various 2-arylaminobenzimidazoles. This methodology is based for the first time on a copper catalyst promoted domino C-N cross-coupling reaction for the generation of 2-arylaminobenzimidazoles. Mechanistic investigations revealed that the synthetic pathway involves a copper-based desulphurization/nucleophilic substitution and a subsequent domino intra and intermolecular C-N cross-coupling reactions. Some of the issues typically encountered during the synthesis of 2-arylaminobezimidazoles, including the use of expensive catalytic systems and the low reactivity of bromo precursors, were addressed using this newly developed copper-catalyzed method. The reaction procedure is simple, generally with excellent substrate tolerance, and provides good to high yields of the desired products.

Copper-catalyzed synthesis of 2-aminophenyl benzothiazoles: a novel approach.

A novel, convenient and efficient protocol for the construction of various 2-aminophenyl benzothiazoles by domino intra- and intermolecular C-N cross-coupling reactions of arylisothioureas with aryl iodides using an inexpensive, air stable and readily available copper catalyst is described. The arylisothioureas were obtained from thiourea via copper promoted desulfurization followed by nucleophilic substitution. In addition, the reactivity of arylhalides and the reaction mechanism have also been studied. The protocol features operational simplicity and a broad substrate scope.