Asymmetric γ-hydroxy nitriles are valuable intermediates because hydrolysis of the
nitriles can result in an intramolecular cyclization to chiral γ-lactones, which have
a variety of biological uses. Starting with an assortment of different aldehydes (alkyl
and aryl) a 4-step synthesis of γ-keto nitriles was developed. These prochiral substrates
were then screened against a library of ketoreductases for their ability to stereoselectively
reduce the carbonyl. Enzymes from the short chain dehydrogenase family showed activity
and these enzymatic reactions were scaled up to produce a diverse set of chiral γ-lactones.
Key words
lactones - enzymes - reduction - asymmetric synthesis - asymmetric catalysis