Čes. slov. farm. 2005, 54(5):201-206

Blockers of β-Adrenergic Receptors - a Group of Chiral Agents Stereoselective Synthesis of β-Blockers

R. Čižmáriková¹, J. Valentová¹, A. J. Hutt², S. Sedláková¹

¹ Farmaceutická fakulta Univerzity Komenského v Bratislave, Katedra chemickej teórie liečiv, SR

² Department of Pharmacy, King's College London, University of London, UK

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.

Keywords: ß-blockers; stereoselective synthesis; arylaminoethanols; aryloxyaminopropanols; enantioselective reduction; chiral precursors

Received: January 31, 2005; Accepted: June 8, 2005; Published: May 1, 2005  Show citation