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
› Author Affiliations
Further Information

Publication History

Received: 04 April 2013

Accepted after revision: 22 May 2013

Publication Date:
25 June 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

 
  • References

  • 1 These authors contributed equally to this work.
  • 2 Wang Y, Tennyson RL, Romo D. Heterocycles 2004; 64: 605
  • 3 Martin VS, Anorbe B, Betancort JM, Martin T, Padron JM, Palazon JM, Ramirez MA, Rodriguez CM, Soler MA. Recent Res. Dev. Org. Chem. 1997; 1: 43
  • 4 Bringmann G, Breuning M, Tasler S. Synthesis 1999; 525
  • 5 Einhorn A. Ber. Dtsch. Chem. Ges. 1883; 16: 2208
  • 6 Yang HW, Romo D. Tetrahedron 1999; 55: 6403
    • 7a Cernuchova P, Mihovilovic MD. Org. Biomol. Chem. 2007; 5: 1715 ; and references cited therein
    • 7b Mihovilovic MD, Muller B, Stanetty P. Eur. J. Org. Chem. 2002; 3711
    • 7c Mihovilovic MD. Curr. Org. Chem. 2006; 10: 1265
  • 8 Moreno-Horn M, Martinez-Rojas E, Gorisch H, Tressl R, Garbe LA. J. Mol. Catal. B: Enzym. 2007; 49: 24
  • 9 Romano D, Contente M, Granato T, Remelli W, Zambelli P, Molinari F. Monatsh. Chem. 2013; 144: 735
  • 10 Zhang X, Xu JH, Xu Y, Pan J. Appl. Microbiol. Biotechnol. 2007; 75: 1087 ; and references cited therein
  • 11 Taylor SK, Chmiel NH, Simons LJ, Vyvyan JR. J. Org. Chem. 1996; 61: 9084
  • 12 Csuk R, Glanzer BI. Chem. Rev. 1991; 91: 49
  • 13 Kaluzna IA, Matsuda T, Sewell AK, Stewart JD. J. Am. Chem. Soc. 2004; 126: 12827 ; and references cited therein
  • 14 Rodriguez S, Kayser MM, Stewart JD. J. Am. Chem. Soc. 2001; 66: 733
  • 15 Kaluzna IA, Feske BD, Wittayanan W, Ghiviriga I, Stewart JD. J. Org. Chem. 2005; 70: 342
  • 16 Feske BD, Kaluzna IA, Stewart JD. J. Org. Chem. 2005; 70: 9654
  • 17 Feske BD, Stewart JD. Tetrahedron: Asymmetry 2005; 16: 3124
  • 18 Nowill RW, Patel TJ, Beasley DL, Alvarez JA, Jackson E, Hizer TJ, Ghiviriga I, Mateer SC, Feske BD. Tetrahedron Lett. 2011; 52: 2440
  • 19 Konaklieva MI, Plotkin BJ. Mini-Rev. Med. Chem. 2005; 5: 73
  • 20 Seebach D, Corey EJ. J. Org. Chem. 1975; 40: 231
  • 21 Stewart JD. Adv. Appl. Microbiol. 2006; 59: 31
  • 22 Marocco CP, Davis EV, Finnell JE, Nguyen P-H, Mateer SC, Ghiviriga I, Padgett CW, Feske BD. Tetrahedron: Asymmetry 2011; 22: 1784