Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β-Blockers (S)-Esmolol and (S)-Penbutolol

The β-blocker (S)-esmolol, has been synthesized in 97% enantiomeric excess and 26% total yield a four-step synthesis, with transesterification step of the racemic chlorohydrin methyl 3-(4-(3-chloro-2-hydroxypropoxy)phenyl)propanoate, catalysed by lipase B from Candida antarctica Syncozymes, Shanghai, China. (S)-penbutolol, 99% 22% yield. 1-chloro-3-(2-cyclopentylphenoxy)propan-2-ol was catalyzed same as used for esmolol building block. We have different bases deprotonation starting phenols, vinyl butanoate acyl donor reactions. reaction times kinetic resolution steps varied 23 to 48 h, were run at 30–38 °C. Specific rotation values confirmed absolute configuration enantiopure drugs, however, an earlier report specific value (S)-esmolol is not consistent our measured values, we here claim that data are correct. Compared previously reported syntheses these two replaced toluene or dichloromethane acetonitrile, flammable acetyl chloride lithium chloride. also reduced amount epichlorohydrin bases, identified dimeric byproducts order obtain higher yields.