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

Abstract 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.