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., Richard R. Watkins, Laura A. Wright, Blair A. Weaver, Ramon C. Hartage, Ion Ghiviriga, Giuseppe Gumina, Brent D. Feske.
"Synthetic Strategy toward γ-Keto Nitriles and Their Biocatalytic Conversion to Asymmetric γ-Lactones."
Synthesis, 45 (15): 2171-2178.
doi: 10.1055/s-0033-1339282 source: https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0033-1339282