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

Linga Banoth, Neeraj Singh Thakur, Jayeeta Bhaumik, Uttam Chand Banerjee

Chirality 2015 Jun

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A new chemoenzymatic route is reported to synthesize acebutolol, a selective β1 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. © 2015 Wiley Periodicals, Inc.

Citation

Linga Banoth, Neeraj Singh Thakur, Jayeeta Bhaumik, Uttam Chand Banerjee. Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β₁-Selective Blocker. Chirality. 2015 Jun;27(6):382-91