Lipase mediated new chemo‐enzymatic synthesis of (RS)‐, (R)‐, and (S)‐bunolol

• Published in: Chirality (New York, N.Y.) N.Y.), 2024-01, Vol.36 (1), p.e23627-n/a
• Main Authors: Patlolla, Ravinder Reddy, Deepthi, Pulivarthi, Raveena, Gajjala, Rosangzuala, Khawlhring, Tejaswini, Somarowthu, Prakasham, Reddy Shetty, Banoth, Linga
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists; biocatalysis; Bunolol; chemo‐enzymatic synthesis; Esters; levobunolol; lipase; Lipase - chemistry; Receptors, Adrenergic, beta; Stereoisomerism
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.23627

The β‐adrenergic receptor blocking agents are an important class of drug molecules. The present study reports a new chemo and chemo‐enzymatic synthetic process for (RS)‐, (R)‐, and (S)‐bunolol, one of the potent β‐adrenergic receptor blocker. In chemo‐enzymatic process, CAL L4777 lipase was employed for enantioselective kinetic resolution to synthesize the enantiopure (R)‐alcohol and (S)‐ester from the corresponding racemic alcohol. Thereafter, the corresponding (R)‐alcohol and deacylated (S)‐ester were treated with tert‐butylamine to produce (S)‐ and (R)‐bunolol, respectively. In chemical approach, epichlorohydrin (RS‐, R‐, and S‐) was used as a starting material via respective (RS)‐, (S)‐, and (R)‐glycidyl ether as intermediates for synthesis of enantiomeric (RS)‐, (R)‐, and (S)‐bunolol. In comparison between two approaches, it was found that the chemo‐enzymatic process was more effective and resulted in enantiomeric excess of 98% with 35% yield. In essence, the authors of the present work report an effective, straightforward chemical and chemo‐enzymatic synthetic technique for the production of enantiopure levobunolol. CAL L4777 enzyme, one of several lipases tested, efficiently catalyzed the reaction with a yield of 35% and an efficiency of 98% at 30°C and acyl donors of cyclohexane and vinyl acetate.