Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β 1 ‐Selective Blocker
Abstract A new chemoenzymatic route is reported to synthesize acebutolol, a selective β 1 adrenergic receptor blocking agent in enantiopure ( R and S ) forms. The enzymatic kinetic resolution strategy was used to synthesize enantiopure intermediates ( R )‐ and ( S )‐N‐(3‐acetyl‐4‐(3‐chloro‐2‐hydroxy...
Published in: | Chirality |
---|---|
Main Authors: | , , , |
Other Authors: | |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Wiley
2015
|
Subjects: | |
Online Access: | http://dx.doi.org/10.1002/chir.22444 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fchir.22444 https://onlinelibrary.wiley.com/doi/pdf/10.1002/chir.22444 |
Summary: | Abstract A new chemoenzymatic route is reported to synthesize acebutolol, a selective β 1 adrenergic receptor blocking agent in enantiopure ( R and S ) forms. The enzymatic kinetic resolution strategy was used to synthesize enantiopure intermediates ( R )‐ and ( S )‐N‐(3‐acetyl‐4‐(3‐chloro‐2‐hydroxypropoxy)phenyl)butyramide from the corresponding racemic alcohols. The results showed that out of eleven commercially available lipase preparations, two enzyme preparations (Lipase A, Candida antarctica , CLEA [CAL CLEA] and Candida rugosa lipase, 62316 [CRL 62316]) act in enantioselective manner. Under optimized conditions the enantiomeric excess of both ( R )‐ and ( S )‐N‐(3‐acetyl‐4‐(3‐chloro‐2‐hydroxypropoxy)phenyl)butyramide were 99.9 and 96.8%, respectively. N‐alkylation of both the ( R ) and ( S ) intermediates with isopropylamine gave enantiomerically pure ( R and S )‐ acebutolol with a yield 68 and 72%, respectively. This study suggests a high yielding, easy and environmentally green approach to synthesize enantiopure acebutolol. Chirality 27:382–391, 2015. © 2015 Wiley Periodicals, Inc. |
---|