Synthesis 2013; 45(15): 2171-2178
DOI: 10.1055/s-0033-1339282
paper
© Georg Thieme Verlag Stuttgart · New York

Synthetic Strategy toward γ-Keto Nitriles and Their Biocatalytic Conversion to Asymmetric γ-Lactones

Sarah E. Franz
a   Department of Chemistry and Physics, Armstrong Atlantic State University, 11935 Abercorn St., Savannah, GA 31419, USA
,
Richard R. Watkins
a   Department of Chemistry and Physics, Armstrong Atlantic State University, 11935 Abercorn St., Savannah, GA 31419, USA
,
Laura A. Wright
a   Department of Chemistry and Physics, Armstrong Atlantic State University, 11935 Abercorn St., Savannah, GA 31419, USA
,
Blair A. Weaver
a   Department of Chemistry and Physics, Armstrong Atlantic State University, 11935 Abercorn St., Savannah, GA 31419, USA
,
Ramon C. Hartage
a   Department of Chemistry and Physics, Armstrong Atlantic State University, 11935 Abercorn St., Savannah, GA 31419, USA
,
Ion Ghiviriga
b   Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA
,
Giuseppe Gumina
c   Department of Chemistry, Georgia Southern University, PO Box 8064, Statesboro, GA 30460, USA   Fax: +1 (912)3443433   eMail: brent.feske@armstrong.edu
,
Brent D. Feske*
a   Department of Chemistry and Physics, Armstrong Atlantic State University, 11935 Abercorn St., Savannah, GA 31419, USA
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Publikationsverlauf

Received: 04. April 2013

Accepted after revision: 22. Mai 2013

Publikationsdatum:
25. Juni 2013 (online)


Abstract

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.

Supporting Information