Blokátory β-adrenergických receptorov – skupina chirálnych liečiv Stereoselektívna syntéza β-blokátorov

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

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