Chemoenzymatic Synthesis of Vitamin B5-Intermediate (R)-Pantolactone via Combined Asymmetric Organo- and Biocatalysis

The combination of an asymmetric organocatalytic aldol reaction with a subsequent biotransformation toward a one-pot-like process for the synthesis of (R)-pantolactone, which to date is industrially produced by a resolution process, is demonstrated. This process consists of an initial aldol reaction catalyzed by readily available L-histidine followed by biotransformation of the aldol adduct by an alcohol dehydrogenase without the need for intermediate isolation. Employing the industrially Attractive starting material isobutanal, a chemoenzymatic three-step process without intermediate purification is established allowing the synthesis of (R)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%.