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Method Article
Liquid chromatographic enantioseparation of racemic beta-blockers via synthesis of diastereomeric amides and (S)-levofloxacin esters as chiral derivatizing agents
Ravi Bhushan
Bhushan's Lab
Corresponding Author
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An effective and simple protocol is described that successfully leads to liquid chromatographic enantioseparation of racemic beta-blockers by derivatization approach (with an example established with (RS)-metoprolol, and verified by using (RS)-atenolol). The chiral derivatizing reagents (CDRs) were synthesised using (S)-levofloxacin as the chiral moiety. The effectiveness of this protocol is not limited to enantioseparation but also to determine absolute configuration of diastereomers. The protocol describes (i) synthesis of CDRs by reaction of (S)-levofloxacin with N-hydroxysuccinimide and N-hydroxybenzotriazole in presence of coupling reagent dicyclohexylcarbodiimide, (ii) synthesis of diastereomers of racemic beta-blockers under microwave irradiation, (iii) separation of diastereomers by HPLC and open column chromatography, and (iv) determination of absolute configuration of diastereomers. The (S)-Lfx based CDRs provide very low limit of detection (LOD) and limit of quantitation (LOQ); they can be successfully used in trace analysis of several other racemic compounds containing amino group (e.g., beta-blockers, amino acids etc).
Keywords
Enantioseparation; Beta-blockers; Diastereomeric amides; (S)-levofloxacin; HPLC
Figure 1
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protocol complete manuscript with figures
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Supplementary Tables Chromatographic separation data Table S1: Chromatographic separation data of diastereomers prepared with CDR-1 and 2.; Table S2 Method validation for HPLC separation of diastereomers of (RS)-Mel prepared with CDR-1 .
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This is a preprint. It has not completed peer review.
Method Article
Liquid chromatographic enantioseparation of racemic beta-blockers via synthesis of diastereomeric amides and (S)-levofloxacin esters as chiral derivatizing agents
Ravi Bhushan
Bhushan's Lab
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 02 Jan, 2018
No community comments so far
Metrics
Comments: 0
HTML Views: ...
Subject Areas
Chemistry
License:
This work is licensed under a CC BY 4.0 License. Read Full License
An effective and simple protocol is described that successfully leads to liquid chromatographic enantioseparation of racemic beta-blockers by derivatization approach (with an example established with (RS)-metoprolol, and verified by using (RS)-atenolol). The chiral derivatizing reagents (CDRs) were synthesised using (S)-levofloxacin as the chiral moiety. The effectiveness of this protocol is not limited to enantioseparation but also to determine absolute configuration of diastereomers. The protocol describes (i) synthesis of CDRs by reaction of (S)-levofloxacin with N-hydroxysuccinimide and N-hydroxybenzotriazole in presence of coupling reagent dicyclohexylcarbodiimide, (ii) synthesis of diastereomers of racemic beta-blockers under microwave irradiation, (iii) separation of diastereomers by HPLC and open column chromatography, and (iv) determination of absolute configuration of diastereomers. The (S)-Lfx based CDRs provide very low limit of detection (LOD) and limit of quantitation (LOQ); they can be successfully used in trace analysis of several other racemic compounds containing amino group (e.g., beta-blockers, amino acids etc).
Figure 1