Blockers of β-Adrenergic Receptors – a Group of Chiral Agents
Stereoselective Synthesis of β-Blockers
ČIŽMÁRIKOVÁ R., VALENTOVÁ J., HUTT A. J.1, SEDLÁKOVÁ S.
Farmaceutická fakulta Univerzity Komenského v Bratislave, Katedra chemickej teórie liečiv, SR 1Department of Pharmacy, King’s College London, University of London, UK |
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Summary:
Besides chromatographic methods and biocatalyzed reactions, another alternative method of obtaining
enantiomeric forms of ß-blockers is stereoselective synthesis. This paper links up with two preceding surveys
concerning ß-blockers – groups of chiral agents and presents a survey of the hitherto published enantioselective
syntheses of (R)- and (S)-enantiomers of β-blockers. In the group of arylaminoethanols, mainly selective
reduction of prochiral ketones in the presence of metallic complexes is used in this type of synthesis.
Enantiomerically pure ß-blockers of the aryloxyaminopropanol type are synthesized by means of a reaction of
pertinent phenols with different chiral precursors, such as (R) and (S)-chloromethyloxirans, (S)-glycidoltosylate,
(S)- or (R)-2,3-O-isopropylideneglyceroltosylate, E-(2S,3S)-3-trimethylsilylglycidol and (S)-3-terc-butyl-5-
-phenyl-oxazolidine-5-ylmethanol. Many of these chiral semiproducts can be prepared from natural substances,
such as D-mannitol and L-ascorbic acid.
Key words:
ß-blockers – stereoselective synthesis – arylaminoethanols – aryloxyaminopropanols – enantioselective
reduction – chiral precursors
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