Development of a novel chemoenzymatic route to enantiomerically enriched β-adrenolytic agents. A case study toward propranolol, alprenolol, pindolol, carazolol, moprolol, and metoprolol.

ABSTRACT: Efficient chemoenzymatic routes toward the synthesis of both enantiomers of adrenergic β-blockers were accomplished by identifying a central chiral building block, which was first prepared using lipase-catalyzed kinetic resolution (KR, Amano PS-IM) as the asymmetric step at a five gram-scale (209 mM conc.). The enantiopure (R)-chlorohydrin (>99% ee) subsequently obtained was used for the synthesis of a series of model (R)-(+)-β-blockers (i.e., propranolol, alprenolol, pindolol, carazolol, moprolol, and metoprolol), which were produced with enantiomeric excess in the range of 96-99.9%. The pharmaceutically relevant (S)-counterpart, taking propranolol as a model, was synthesized in excellent enantiomeric purity (99% ee) via acetolysis of the respective enan

SUBMITTER: Borowiecki P 

PROVIDER: S-EPMC9364081 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature