Synthetic strategy toward γ-KETO NITRILES and their Biocatalytic conversion to asymmetric γ-lactones
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.
Franz, Sarah E.,Watkins, Richard R.,Wright, Laura A.,Weaver, Blair A.,Hartage, Ramon C.,Ghiviriga, Ion,Gumina, Giuseppe,Feske, Brent D.