Fast liquid chromatography for racemic atenolol acetate separation—The analytical protocol

Abstract

Kinetic resolution of (R,S)-atenolol is a faster strategy to produce (S)-atenolol. Since this racemate is a less soluble compound, resolution of its ester offers high concentrations in the process. A good analytical method is required to observe the enantiomer concentrations. This paper described application of ultra-fast liquid chromatography on the atenolol ester separation using different resolution media and analytical procedures. Chiralcel OD column resolved the ester. The chromatograms indicated different characteristics of the process. The enantiomers could be recognized by the column in less than 1 (one) hour. Symmetrical peaks were obtained, but several procedures produced peaks with wide bases and slanted baselines. Efficient enantioresolution was obtained at high mobile phase flow rate, decreased concentration of amine-type modifier, but increased alcohol content in the mobile phase. High UV detection wavelength was required. At 1.0 mL/min, the (90/10/0.5) composition resulted α = 1.46 and R = 0.9998 that were good separation.

Kinetic resolution of (RS)-1-chloro-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol: a metoprolol intermediate and its validation through homology model of Pseudomonas fluorescens lipase

“…During the course of the reaction, the enantioselectivity gradually decreased and PFL exhibited non-selective behaviour. In a recent study on kinetic resolution of racemic atenolol, PFL has been reported to give (S)-enantiomer in 24 h. 36 In another study, PFL catalyzed the kinetic resolution of some novel antifungal Nsubstituted benzimidazole derivatives in more than 72 h. 37 Thus, the rapid action of PFL on (RS)-4 with high degree of enantioselectivity and rate of conversion reported here is suggestive of strong interaction between (RS)-4 and PFL, thereby revealing a better chemoenzymatic process that could be used for the synthesis of enantiopure metoprolol in a shorter time.…”

Covalent immobilization of lipases on activated hollow silica microspheres

“…Surface-modified silica gel-based particles proved to be efficient supports in our practice for the immobilization of several lipases [21][22][23][24][25][26]. Therefore, in this study our aim was to extend the immobilization of further lipases [Lipase AK from Pseudomonas fluorescens (Lipase AK), Lipase PS from Burkholderia cepacia (Lipase PS) and Lipase from Candida rugosa (CrL)] using bisepoxide-activated mesoporous hollow silica microspheres to produce efficient biocatalysts for kinetic resolution of secondary alcohols.…”