Chemoenzymatic Synthesis of Vitamin B5-Intermediate (<i>R</i>)‑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 (<i>R</i>)-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 (<i>R</i>)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%