A New Route from D-Mannitol to Enantiomerically Pure (S)-1-Alkylamino-3-aryloxy-2-propanols.

Lamm, Bo; Ankner, Kjell; Frantsi, Marianne; Aasen, Arne Jørgen; Fischer, G. W.

doi:10.3891/acta.chem.scand.41b-0202

Cited by 8 publications

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“…Drugs S, R and racemic metoprolol were obtained from the department of Organic Chemistry, AB Hiissle. The method for synthesis of the S-enantiomer of metoprolol has recently been described (Lamm et al, 1987). The R-antipode used in the present work was prepared from D-mannitol via (R)-1-Omethanesulphonyl-2,3-O-isopropylidene-glycerol, following a previously published method (Danilevicz & Kemp, 1973) with one modification, the cyclic sulphite was used instead of the primary tosylate of the 1-aryloxy-2,3-propranediol.…”

Section: In Vivo Experimentsmentioning

confidence: 99%

“…The techniques for stereoselective synthesis of compounds have markedly improved in recent years. The use of optically pure precursors makes it possible to synthesize compounds with a high degree of enantiomeric purity (Lamm et al, 1987). With this technique, the S-and R-forms of metropolol with an enantiomeric purity of >99.2% (S) and >99.9% (R) were recently synthesized by the Department of Organic Chemistry, AB Hassle.…”

Section: Introductionmentioning

confidence: 99%

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The β₁ and β₂‐adrenoceptor affinity and β₁‐blocking potency of S‐ and R‐metoprolol

Wahlund¹,

Nerme²,

Abrahamsson³

et al. 1990

British J Pharmacology

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1 The f-adrenoceptor affinity and blocking potency of the two enantiomers and the racemate of metoprolol were investigated in vitro, by use of a receptor-binding technique, and in vivo in the anaesthetized cat.2 The enantiomeric purity of the S-and R-form was: > 99.2% and > 99.9%, respectively.3 The fl1-and fl2-adrenoceptor affinity (-log equilibrium dissociation-constant) of the enantiomers was determined from competition binding experiments (radioligand: [125I]4S)-pindolol) performed in membranes prepared from the guinea-pig left ventricular free wall (predominantly fl1) and soleus muscle (#2)The fl1-adrenoceptor affinity was (means + s.d.): 7.73 + 0.10 and 5.00 + 0.06 for the S-and R-form of metoprolol, respectively. The corresponding values for fl2-adrenoceptors were 6.28 + 0.06 (S) and 4.52 + 0.09 (R). Thus, the difference in affinity for the two enantiomers was greater on fl1-(about 500) than on fl2-adrenoceptors (about 50). The #1-adrenoceptor selectivity of the S-form (about 30) was similar to that of the racemic metoprolol, while the R-form was almost non-selective (3 fold fl1-selective). 4 In the anaesthetized cat, the (-log) intravenous doses (pmolkg-1) of S-and R-metoprolol causing a 50% reduction (ED50) in the heart rate response to sympathetic nerve stimulation were determined. The doses inducing a 25% depression (DD25) of the basal myocardial contractility were also estimated. For the two enantiomers, the fl-blocking potency (-log ED5o) was 7.04 + 0.16 (S) and 4.65 + 0.16 (R). A significant cardiodepressive effect was observed at high doses (-log DD25): 4.18 + 0.20 (S) and 4.08 + 0.10 (R).5 It is concluded that the binding of metoprolol to fl1-adrenoceptors has a stricter steric requirement than that for the binding of this fl-blocker to f2-adrenoceptors. Furthermore, the non-specific cardiodepressive effect of metoprolol was observed at equally high doses for the two enantiomers.

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Section: In Vivo Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The β₁ and β₂‐adrenoceptor affinity and β₁‐blocking potency of S‐ and R‐metoprolol

Wahlund¹,

Nerme²,

Abrahamsson³

et al. 1990

British J Pharmacology

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Optically Active Glycerol Derivatives

Mulzer

Altenbach

Braun

et al. 2003

Organic Synthesis Set

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Optically Active Glycerol Derivatives

1990

Organic Synthesis Highlights

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A New Route from D-Mannitol to Enantiomerically Pure (S)-1-Alkylamino-3-aryloxy-2-propanols.

Cited by 8 publications

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The β₁ and β₂‐adrenoceptor affinity and β₁‐blocking potency of S‐ and R‐metoprolol

The β₁ and β₂‐adrenoceptor affinity and β₁‐blocking potency of S‐ and R‐metoprolol

Optically Active Glycerol Derivatives

Optically Active Glycerol Derivatives

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A New Route from D-Mannitol to Enantiomerically Pure (S)-1-Alkylamino-3-aryloxy-2-propanols.

Cited by 8 publications

References 0 publications

The β1 and β2‐adrenoceptor affinity and β1‐blocking potency of S‐ and R‐metoprolol

The β1 and β2‐adrenoceptor affinity and β1‐blocking potency of S‐ and R‐metoprolol

Optically Active Glycerol Derivatives

Optically Active Glycerol Derivatives

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The β₁ and β₂‐adrenoceptor affinity and β₁‐blocking potency of S‐ and R‐metoprolol

The β₁ and β₂‐adrenoceptor affinity and β₁‐blocking potency of S‐ and R‐metoprolol