Microchemical enantioseparation of betaxolol and orciprenaline by reversed phase HPLC

Abstract

Enantioseparation of (RS)-orciprenaline and (RS)-betaxolol was achieved by synthesizing their diastereomeric derivatives with chiral derivatizing reagents prepared on a cyanuric chloride platform. There were three dichloro-triazine derivatives with amino acid amides as chiral auxiliaries and three monochlorotriazine derivatives with methoxy as achiral moiety and amino acid amides as chiral auxiliaries in cyanuric chloride. A total of 12 pairs of diastereomeric derivatives were synthesized under microwave irradiation and were separated using reversed phase high-performance liquid chromatography by applying different mobile phases on a C 18 column in gradient eluting mode with ultraviolet detection at 230 nm. Resolutions were compared and interpreted on the basis of structure of chiral auxiliaries. Besides, diastereomeric derivatives were separated by open column chromatography and the samples so obtained were used for confirmation of their elution order and configuration by 1 H-NMR spectroscopy. In addition, lowest energy optimized structures of diastereomeric derivatives were developed using the density functional theory based Gaussian software that were interpreted to supplement the absolute configurations. The method validation was carried out for detection limit, linearity, accuracy, and precision. Limits of detection were 0.005 and 0.007 µg/mL.

Reversed‐phase‐HPLC enantioseparation and control of enantiomeric purity of duloxetine using a new chiral reagent and recovery of enantiomers

“…Resolution parameters of diastereomeric derivatives show superiority of the present method, particularly over chiral HPLC, in terms of higher resolution value (Davadra et al, 2011;Rane & Shinde, 2008;Yang et al, 2007). As reported earlier (Nagar et al, 2020), MeCN provided a higher elution power than MeOH in RP chromatography. MeCN provides reduced noise, higher sensitivity, and increased peak intensity (signal-to-noise ratio) (Li, 1992).…”

′Ab Ovo′ Chiral Phases and Chiral Reagents for Liquid Chromatographic Separation and Isolation of Enantiomers

“…Reversed phase HPLC enantioseparation of (RS)-orciprenaline, and betaxolol was achieved as their diastereomeric derivatives synthesized [94] with DCT reagents (20), ( 21) and ( 23), and MCT reagents ( 25), ( 26) and (28). Scheme 1A shows reactions for the formation of DCT ( 23) and diastereomeric derivatives of (RS)-orciprenaline.…”

“…Various β-adrenergic blocking agents mentioned in this paper, and explained on the similar lines, include, diastereomeric derivatives of (i) (RS)-betaxolol prepared with Npx-Btz [as (S)-Npx-(R)-betaxolol] and [(S)-Npx-(S)-betaxolol], [100] (ii) (RS)-orciprenaline, betaxolol and propranolol prepared with DFDNB based CDRs with S-methyl-L-Cysteine, (S)-(+)-1-cyclohexylethylamine and (R)-(+)-α-methyl benzylamine as chiral auxiliaries, [41] (RS)-isoxsuprine prepared with (1), (3) and another CDR having S-Benzyl-L-cysteine as chiral auxiliary in DFDNB, [40] (iii) (RS)-propranolol prepared with (S)-Lfx based CDRs, [105] (iv) (RS)-propranolol, metoprolol and atenolol prepared with the (S)-Kpf based CDRs, [104] (v) (RS)salbutamol, carvedilol, bisoprolol and betaxolol prepared with (S)-Kpf based CDRs, [109] and prepared with (S)-Lfx based CDRs, [105] (RS)-orciprenaline, and betaxolol prepared with DCT reagents (20), ( 21) and (23), and MCT reagents (25), ( 26) and ( 28). [94] 9. Mechanism for Direct Separation in TLC…”