Resolution of the enantiomers of drugs containing amino alcohol structure after derivatization with bromoacetic acid

Pierer, B.; Wendelin, W.

doi:10.1002/chir.530040512

Cited by 17 publications

(11 citation statements)

References 6 publications

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“…Moreover, it is the key functionality in beta‐blockers and adrenergic drugs. For many beta‐blockers, the pharmacological activity is attributed to the S‐ enantiomers and for adrenergic drugs it is the R‐ enantiomers . Recently, Mullie et al .…”

Section: Introductionmentioning

confidence: 88%

“…For many beta-blockers, the pharmacological activity is attributed to the S-enantiomers and for adrenergic drugs it is the R-enantiomers. [6] Recently, Mullie et al reported that the enantiomeric pairs of 4-amino alcohol quinoline derivatives showed difference in the malarial activity, i.e. S-enantiomer showed 2-15 folds better activity than its counter form (Renantiomer).…”

Section: Introductionmentioning

confidence: 99%

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Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

et al. 2014

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The enantiomeric differentiation of a series of chiral β-amino alcohols (A) is attempted, for the first time, by applying the kinetic method using L-proline, L-tryptophan, 4-iodo-L-phenylalanine or 3, 5-diiodo-L-tyrosine as the chiral references (Ref) and Cu(2+) or Ni(2+) ion (M) as the central metal ion. The trimeric diastereomeric adduct ions, [M+(Ref)2+A-H](+), formed under electrospray ionization conditions, are subjected for collision-induced dissociation (CID) experiments. The products ions, formed by the loss of either a reference or an analyte, detected in the CID spectra are evaluated for the enantiomeric differentiation. All the references showed enantiomeric differentiation and the R(chiral) values are better for the aromatic alcohols than for aliphatic alcohols. Notably, the R(chiral) values of the aliphatic amino alcohols enhanced when Ni(2+) is used as the central metal ion. The experimental results are well supported by computational studies carried out on the diastereomeric dimeric complexes. The computational data of amino alcohols is correlated with that of amino acids to understand the structural interaction of amino alcohols with reference molecule and central metal ion and their role on the stabilization of the dimeric complexes. Application of flow injection MS/MS method is also demonstrated for the enantiomeric differentiation of the amino alcohols.

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Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

et al. 2014

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“…Generally, the cardioselectivity and β‐blocking activity of S ‐enantiomers of aryloxypropanol amine is 50–500 times more than the R ‐enantiomers. Several strategies for the synthesis of acebutolol have been reported in the literature (Scheme ) …”

Section: Methodsmentioning

confidence: 99%

“…Several strategies for the synthesis of acebutolol have been reported in the literature (Scheme 1). [22][23][24][25] Only a few reports are available for the enantiopure synthesis of this drug molecule. One of the reported strategies (strategy 1) uses chiral halohydrin or glyceryl acetonide to convert phenol 3 to enantiopure halohydrin 5.…”

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confidence: 99%

Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β₁‐Selective Blocker

et al. 2015

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A new chemoenzymatic route is reported to synthesize acebutolol, a selective β1 adrenergic receptor blocking agent in enantiopure (R and S) forms. The enzymatic kinetic resolution strategy was used to synthesize enantiopure intermediates (R)- and (S)-N-(3-acetyl-4-(3-chloro-2-hydroxypropoxy)phenyl)butyramide from the corresponding racemic alcohols. The results showed that out of eleven commercially available lipase preparations, two enzyme preparations (Lipase A, Candida antarctica, CLEA [CAL CLEA] and Candida rugosa lipase, 62316 [CRL 62316]) act in enantioselective manner. Under optimized conditions the enantiomeric excess of both (R)- and (S)-N-(3-acetyl-4-(3-chloro-2-hydroxypropoxy)phenyl)butyramide were 99.9 and 96.8%, respectively. N-alkylation of both the (R) and (S) intermediates with isopropylamine gave enantiomerically pure (R and S)- acebutolol with a yield 68 and 72%, respectively. This study suggests a high yielding, easy and environmentally green approach to synthesize enantiopure acebutolol.

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“…Several authors report on the indirect separation of amino alcohol enantiomers by ligand-exchange HPLC (LE-HPLC) using different derivatization reagents [1][2][3]. Direct separation of amino alcohol enantiomers by LE-HPLC often causes problems, since the pH optimum for complexation for amino alcohols is at high pH.…”

Section: Introductionmentioning

confidence: 99%

Chiral separation of sympathomimetics and β‐blockers by ligand‐exchange CE using Cu(II) complexes of L‐tartaric acid and L‐threonine as chiral selectors

et al. 2007

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This paper deals with the use of Cu(II) complexes of L-tartaric acid or L-threonine as selectors for the chiral separation of drugs containing amino alcohol structure by ligand-exchange CE. Using Cu(II) ions as a complexing agent, a series of sympathomimetics and beta-blockers were resolved. It was found that the resolution strongly depends on selector concentration and pH. The optimum pH for complexation was 12.

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Resolution of the enantiomers of drugs containing amino alcohol structure after derivatization with bromoacetic acid

Abstract: The separation of the enantiomers of drugs containing an amino alcohol structure like adrenergic drugs or 0-blockers is described. The compounds are resolved on chiral ligand-exchange chromatography phases after derivatization with bromoacetic acid. 0 1992 Wiley-Liss, Inc.

Cited by 17 publications

References 6 publications

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β₁‐Selective Blocker

Chiral separation of sympathomimetics and β‐blockers by ligand‐exchange CE using Cu(II) complexes of L‐tartaric acid and L‐threonine as chiral selectors

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Resolution of the enantiomers of drugs containing amino alcohol structure after derivatization with bromoacetic acid

Abstract: The separation of the enantiomers of drugs containing an amino alcohol structure like adrenergic drugs or 0-blockers is described. The compounds are resolved on chiral ligand-exchange chromatography phases after derivatization with bromoacetic acid. 0 1992 Wiley-Liss, Inc.

Cited by 17 publications

References 6 publications

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β1‐Selective Blocker

Chiral separation of sympathomimetics and β‐blockers by ligand‐exchange CE using Cu(II) complexes of L‐tartaric acid and L‐threonine as chiral selectors

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Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β₁‐Selective Blocker