Single enantiomeric β-blockers—The existing technologies

Agustian, Joni; Kamaruddin, Azlina Harun; Bhatia, Subhash

doi:10.1016/j.procbio.2010.06.022

Cited by 47 publications

(38 citation statements)

References 220 publications

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“…Both R-and S-enantiomers for each compound were considered for the calculations as beta-blockers are typically prepared and sold as racemic mixtures. [17] The equilibrium conformer of each molecule protonated at each basic site was calculated at the ground state using the Merck molecular force field. This conformer was then used to calculate the optimised geometry at the HF/6-31 G* level of theory (one O-protonated molecule for both esmolol and metoprolol failed to produce an optimised equilibrium geometry, and thus were excluded from the dataset).…”

Section: Compoundmentioning

confidence: 99%

The low‐energy collision‐induced dissociation product ion spectra of protonated beta‐blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions

2011

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The low-energy collision-induced dissociation product ion spectra of protonated beta-blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions Beta-blockers are a class of pharmaceutical compounds used in the therapy of numerous cardiovascular disorders including the treatment of hypertension, [1,2] for cardioprotection post-myocardial infarction, [3] in the management of angina pectoris [4] and for the regulation of heart rate in patients with cardioarrhythmia.[5] They are also used in the treatment of chronic kidney disease [6] and the relief of intraocular pressure in glaucoma sufferers. [7] A recent study in our laboratories involved the investigation of the lowenergy collision-induced dissociation (CID) pathways of protonated beta-blockers on a quadrupole ion trap (QIT) mass spectrometer and revealed an interesting analogy to fragmentation behaviour under electron ionisation (EI) conditions. Fourteen beta-blockers (acebutolol, alprenolol, atenolol, betaxolol, carteolol, celiprolol, esmolol, levobunolol, metoprolol, nadolol, oxprenolol, pindolol, propranolol and timolol) were provided by Pfizer Global Research and Development (Sandwich, UK). Solutions were prepared at 10 mg mL À1 in either liquid chromatography-mass spectrometry grade methanol and analytical grade formic acid [99.9:0.1, v/v] (Fisher Scientific UK Ltd., Loughborough, UK) or in >99.5% deuterated methanol and 99.5% deuterated formic acid [99.9:0.1, v/v] (Apollo Scientific Limited, Stockport, UK). 'In-time' low-energy CID product ion spectra of either the protonated or fully exchanged, deuterated molecule (i.e. all acidic protons exchanged for deuterons) for each compound were acquired using a LCQ Classic QIT mass spectrometer (Thermo Fisher Scientific, San Jose, CA, USA). Positive ion electrospray ionisation was performed by infusing the solutions directly into the ion source at a constant flow rate of 3 mL min À1. Nitrogen was used as the sheath and auxiliary gas. The ion source conditions were: sheath gas, 25 arbitrary units; auxiliary gas, 0 arbitrary units; spray voltage, 4.5 kV; capillary voltage, 10 V; capillary temperature, 160 C; tube lens offset, À5 V. Lowenergy CID product ion spectra were acquired using an isolation width of 6 m/z units (1 m/z unit for the solution-phase H/D exchange experiments to ensure only the fully exchanged, deteurated molecule was selected to undergo CID), an activation Q of 0.250 and an activation time of 30 ms. The normalised collision energy was set to either 50% or 60% to cause complete dissociation of the precursor ion.[8] Acquisitions were performed for 20 scans with WideBand activation both on and off.[8] Helium was used as the buffer gas. Data acquisition was performed using XCalibur version 1.2 (Thermo Fisher Scientific, San Jose, CA, USA).A common structural feature of beta-blockers is the oxypropanolamine side chain, which can either terminate in an isopropyl or a tert-butyl group.[9] The compounds in this study were split into two sets (Compound sets 1 and 2, Figs...

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Section: Compoundmentioning

confidence: 99%

The low‐energy collision‐induced dissociation product ion spectra of protonated beta‐blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions

2011

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“…Recently, formation of the enantiomer was offered through an enzymatic transesterification reaction of a racemic alcohol, precursor of the ( S )‐atenolol, in ionic liquids . Since the racemic atenolol is available in markets, the kinetic resolution is the faster strategy to produce the single enantiomer than asymmetric syntheses …”

Section: Introductionmentioning

confidence: 99%

Factors screening to statistical experimental design of racemic atenolol kinetic resolution via transesterification reaction in organic solvent using free Pseudomonas fluorescens lipase

2017

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As the (R)‐enantiomer of racemic atenolol has no β‐blocking activity and no lack of side effects, switching from the racemate to the (S)‐atenolol is more favorable. Transesterification of racemic atenolol using free enzymes investigated as a resource to resolve the racemate via this method is limited. Screenings of enzyme, medium, and acetyl donor were conducted first to give Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate. A statistical design of the experiment was then developed using Central Composite Design on some operational factors, which resulted in the conversions of 11.70–61.91% and substrate enantiomeric excess (ee) of 7.31–100%. The quadratic models are acceptable with R2 of 95.13% (conversion) and 89.63% (ee). The predicted values match the observed values reasonably well. Temperature, agitation speed, and substrate molar ratio factor have low effects on conversion and ee, but enzyme loading affects the responses highly. The interaction of temperature–agitation speed and temperature–substrate molar ratio show significant effects on conversion, while temperature–agitation speed, temperature–substrate molar ratio, and agitation speed–substrate molar ratio affect ee highly. Optimum conditions for the use of Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate were found at 45°C, 175 rpm, 2000 U, and 1:3.6 substrate molar ratio.

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“…1 Aryloxypropanolamines are extensively used as precursors for the synthesis of a varieties of cardiovas cular drugs used in the treatment of hypertension, myocardial infarction, arrhythmias, angina pectoris and ischemic heart disease [1]. Aryloxypropanola mines are also used for the synthesis of drugs for other than cardiovascular diseases [2−6].…”

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“…A method to syn thesize enantiopure 1 bromo 3 chloro 2 propanol to be then derivatized to enantiopure aryloxypropanola mine may be a better choice for the synthesis of various β blockers. This process has the following advantages over the existing methods: a-most of the β blockers may be produced by synthesizing one enantiopure intermediate 1 bromo 3 chloro 2 propanol; b-no 1 The article is published in the original. need to use different catalysts for synthesizing differ ent β blockers; c-minimization of reaction steps, rendering the process simple and convenient with excellent selectivity; d-this intermediate may be used to synthesize drugs other than β antagonists such as, protein tyrosine phosphatase 1 B inhibitor [10], anticancer [11], cough suppressant, expectorant, skel etal muscle relaxant, anti asthmatic, antigout, spas molytic [12], antiviral, antimicrobial [13], and γ amino β hydroxybutyric acid; e-this intermediate may also be used to synthesize new bioactive com pounds [14].…”

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Development and validation of HPLC method for the resolution of derivatives of 1-bromo-3-chloro-2-propanol: a novel chiral building block for the synthesis of pharmaceutically important compounds

Banoth¹,

Pujala²,

Chakraborti³

et al. 2014

J Anal Chem

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The methods for the separation of racemic compounds [(RS) 1 bromo 3 chloro 2 propanol, (RS) 1 bromo 3 chloropropan 2 yl acetate] into the corresponding enantiomers were tried to develop in high performance liquid chromatography in a single injection mode. In the case of HPLC, both the reversed (Phenomenex Lux 5u cellulose 1, Lux 5u cellulose 2, Lux 5u amylose 1) and normal phase (Chiralcel OJH, ODH, ADH) chiral columns were used for this purpose. HPLC methods could not resolute the desired enan tiomers. However, phenoxy derivatives of (RS) 1 bromo 3 chloro 2 propanol and (RS) 1 bromo 3 chloro propan 2 yl acetate were separated by normal phase (ODH) column using a mobile phase consisting of n hexane and isopropanol (80 : 20) at a flow rate of 0.5 mL/min (25°C) and detected at 254 nm. The method was validated for linearity, range, accuracy and precision. The developed method was applied for monitoring the progress of lipase catalyzed enantioselective synthesis of (S) 1 bromo 3 chloropropan 2 yl acetate from (RS) 1 bromo 3 chloro 2 propanol. All the analytes were synthesized chemically.Keywords: (RS) 1 bromo 3 chloro 2 propanol, (RS) 1 bromo 3 chloropropan 2 yl acetate, chiral HPLC, ODH column

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Single enantiomeric β-blockers—The existing technologies

Cited by 47 publications

References 220 publications

The low‐energy collision‐induced dissociation product ion spectra of protonated beta‐blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions

The low‐energy collision‐induced dissociation product ion spectra of protonated beta‐blockers reveal an analogy to fragmentation behaviour under electron ionisation conditions

Factors screening to statistical experimental design of racemic atenolol kinetic resolution via transesterification reaction in organic solvent using free Pseudomonas fluorescens lipase

Development and validation of HPLC method for the resolution of derivatives of 1-bromo-3-chloro-2-propanol: a novel chiral building block for the synthesis of pharmaceutically important compounds

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