Lipase-catalyzed green synthesis of enantiopure atenolol

Abstract

A new green route is proposed for the synthesis of enantiopure atenolol (a β1-blocker).

Factors screening to statistical experimental design of racemic atenolol kinetic resolution via transesterification reaction in organic solvent using free Pseudomonas fluorescens lipase

“…Most of the employed enzymes were found converting both the atenolol enantiomers. Although a previous study found that the immobilized CALB is a prospective enzyme, the enzyme changed both atenolol enantiomers as most other biocatalysts. Previously, lipase PS immobilized on diatomite earth (lipase PS‐D) had successfully catalyzed the kinetic resolution of the racemic atenolol, but the free‐form lipase Amano PS from Burkholderia cepacia used in the experiments was not able to resolve the compound.…”

“…The second method resolves the available racemic atenolol via chromatographic resolutions, which employ many types of chiral selectors, microbial fermentation of the racemate or its derivative, and enantioselective esterification or hydrolysis of the racemate using immobilized enzymes . Recently, formation of the enantiomer was offered through an enzymatic transesterification reaction of a racemic alcohol, precursor of the ( S )‐atenolol, in ionic liquids . Since the racemic atenolol is available in markets, the kinetic resolution is the faster strategy to produce the single enantiomer than asymmetric syntheses …”

Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β1‐Selective Blocker

“…Chiral HPLC and optical rotation analysis was used to determine the optical purity of synthesized compounds. Here, the nucleophilic ring opening of oxirane at the least substituted carbon atom followed by nucleophilic displacement of chlorine atom through S N (concerted) mechanism (Scheme ) may have been responsible for the inversion of configuration . Following the same mechanism, ( R )‐ 11 can be prepared from ( S )‐ 4 .…”

Kinetic resolution of a b-adrenolytic drug with the use of lipases as enantioselective biocatalysts

“…Although the two enantiomers of b-blockers feature the same chemical and physical properties in an achiral environment, they differ in pharmacological activity. It has been reported by many studies that only the S-enantiomer of b-blockers has the desired therapeutic effect, whereas the administration of the racemate may cause dangerous side effects, such as bronchoconstriction or diabetes (6)(7)(8)(9). Nevertheless, b-blockers are still commercially available and mainly used in medicine as racemates.…”