Skip to main content
SpringerLink
Log in

Biocatalytic deracemisation of aliphatic β-hydroxy esters: Improving the enantioselectivity by optimisation of reaction parameters

  • Biocatalysis
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Optically pure aliphatic β-hydroxy esters were prepared from their racemates by deracemisation using the biocatalyst Candida parapsilosis ATCC 7330. High optical purity (up to >99 %) and good yields (up to 71 %) of the product secondary alcohols were obtained. This study highlights the importance of optimization of reaction conditions using ethyl-3-hydroxybutanoate as the model substrate to improve the enantioselectivity (enantiomeric excess from 9 to 98 %). The present study emphasises the broad substrate scope of the biocatalyst towards deracemisation. This is the first report of Candida parapsilosis ATCC 7330-mediated deracemisation of various alkyl-3-hydroxybutanoates to produce either the (R)-enantiomers (methyl, ethyl, propyl, butyl, t-butyl, allyl-3-hydroxybutanoates) or (S)-enantiomers (pentyl, iso-amyl and iso-propyl-3-hydroxybutanoates).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Zhou BN, Gopalan AS, VanMiddlesworth F, Shieh WR, Sih CJ (1983) Stereochemical control of yeast reductions. 1. Asymmetric synthesis of L-carnitine. J Am Chem Soc 105(18):5925–5926

    Article  CAS  Google Scholar 

  2. Georg GI, Kant J (1988) An asymmetric synthesis of carbapenem antibiotic (+)-PS-5 from ethyl 3-hydroxybutanoate. J Org Chem 53(3):692–695

    Article  CAS  Google Scholar 

  3. Asako H, Shimizu M, Itoh N (2009) Biocatalytic production of (S)-4-bromo-3-hydroxybutyrate and structurally related chemicals and their applications. Appl Microbiol Biotechnol 84(3):397–405

    Article  CAS  PubMed  Google Scholar 

  4. Allegrone G, Barbeni M (1992) Identification of volatile components of caja fruit (Spondias lutea L.) and chiral analysis of 3-hydroxy aliphatic esters. Flavour Frag J 7 (6):337-342

  5. Seebach D, Züger M (1982) Über die depolymerisierung von Poly-(R)-3-hydroxy-buttersäureester (PHB). Helv Chim Acta 65(2):495–503

    Article  CAS  Google Scholar 

  6. Mahob RJ, Babin R, ten Hoopen GM, Dibog L, Yede, Hall DR, Bilong CF (2011) Field evaluation of synthetic sex pheromone traps for the cocoa mirid Sahlbergella singularis (Hemiptera: Miridae). Pest Manag Sci 67(6):672–676

    Article  CAS  PubMed  Google Scholar 

  7. Noyori R, Ohkuma T, Kitamura M, Takaya H, Sayo N, Kumobayashi H, Akutagawa S (1987) Asymmetric hydrogenation of β-keto carboxylic esters. A practical, purely chemical access to β-hydroxy esters in high enantiomeric purity. J Am Chem Soc 109(19):5856–5858

    Article  CAS  Google Scholar 

  8. Corey EJ, Helal CJ (1998) Reduction of carbonyl compounds with chiral oxazaborolidine catalysts: a new paradigm for enantioselective catalysis and a powerful new synthetic method. Angew Chem Int Ed 37(15):1986–2012

    Article  CAS  Google Scholar 

  9. Fuganti C, Grasselli P, Casati P, Carmeno M (1985) On the steric course of baker’s yeast mediated reduction of alkyl 4-azido- and 4-bromo-3-oxobutyrate. synthesis of (R)- and (S)-carnitin. Tetrahedron Lett 26(1):101–104

    Article  CAS  Google Scholar 

  10. Nakamura K, Inoue Y, Matsuda T, Ohno A (1995) Microbial deracemization of 1-arylethanol. Tetrahedron Lett 36(35):6263–6266

    Article  CAS  Google Scholar 

  11. Fishman A, Eroshov M, Dee-Noor SS, van Mil J, Cogan U, Effenberger R (2001) A two-step enzymatic resolution process for large-scale production of (S)- and (R)-ethyl-3-hydroxybutyrate. Biotechnol Bioeng 74(3):256–263

    Article  CAS  PubMed  Google Scholar 

  12. Strauss UT, Felfer U, Faber K (1999) Biocatalytic transformation of racemates into chiral building blocks in 100% chemical yield and 100% enantiomeric excess. Tetrahedron Asymmetry 10(1):107–117

    Article  CAS  Google Scholar 

  13. Strauss UT, Faber K (1999) Deracemization of (±)-mandelic acid using a lipase-mandelate racemase two-enzyme system. Tetrahedron Asymmetry 10(21):4079–4081

    Article  CAS  Google Scholar 

  14. Nie Y, Xu Y, Mu XQ (2004) Highly enantioselective conversion of racemic 1-phenyl-1,2-ethanediol by stereoinversion involving a novel cofactor-dependent oxidoreduction system of Candida parapsilosis CCTCC M203011. Org Process Res Dev 8(2):246–251

    Article  CAS  Google Scholar 

  15. Ishige T, Honda K, Shimizu S (2005) Whole organism biocatalysis. Curr Opin Chem Biol 9:174–180

    Article  CAS  PubMed  Google Scholar 

  16. Tao J, Xu JH (2009) Biocatalysis in development of green pharmaceutical processes. Curr Opin Chem Biol 13(1):43–50

    Article  CAS  PubMed  Google Scholar 

  17. Zhang BB, Lou WY, Chen WJ, Zong MH (2012) Efficient asymmetric reduction of 4-(Trimethylsilyl)-3-butyn-2-one by Candida parapsilosis cells in an ionic liquid-containing system. PLoS One 7(5):e37641

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Houng JY, Liao J-H, Wu JY, Shen SC, Hsu HF (2007) Enhancement of asymmetric bioreduction of ethyl 4-chloro acetoacetate by the design of composition of culture medium and reaction conditions. Process Biochem 42(1):1–7

    Article  CAS  Google Scholar 

  19. Chen XH, Lou WY, Zong MH, Smith T (2011) Optimization of culture conditions to produce high yields of active Acetobacter sp. CCTCC M209061 cells for anti-Prelog reduction of prochiral ketones. BMC Biotechnol 11(1):110–121

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Wang XT, Chen XH, Xu Y, Lou WY, Wu H, Zong MH (2013) Biocatalytic anti-Prelog stereoselective reduction of ethyl acetoacetate catalyzed by whole cells of Acetobacter sp. CCTCC M209061. J Biotechnol 163(3):292–300

    Article  CAS  PubMed  Google Scholar 

  21. Kaliaperumal T, Gummadi SN, Chadha A (2011) Synthesis of both enantiomers of ethyl-4-chloro-3-hydroxbutanoate from a prochiral ketone using Candida parapsilosis ATCC 7330. Tetrahedron Asymmetry 22(14–15):1548–1552

    Article  CAS  Google Scholar 

  22. Baskar B, Pandian NG, Priya K, Chadha A (2005) Deracemisation of aryl substituted α-hydroxy esters using Candida parapsilosis ATCC 7330: effect of substrate structure and mechanism. Tetrahedron 61(52):12296–12306

    Article  CAS  Google Scholar 

  23. Padhi SK, Chadha A (2005) Deracemisation of aromatic β-hydroxy esters using immobilised whole cells of Candida parapsilosis ATCC 7330 and determination of absolute configuration by 1H NMR. Tetrahedron Asymmetry 16(16):2790–2798

    Article  CAS  Google Scholar 

  24. Titu D, Chadha A (2008) Enantiomerically pure allylic alcohols: preparation by Candida parapsilosis ATCC 7330 mediated deracemisation. Tetrahedron Asymmetry 19(14):1698–1701

    Article  CAS  Google Scholar 

  25. Saravanan T, Chadha A (2010) Biocatalytic deracemization of alkyl-2-hydroxy-4-arylbut-3-ynoates using whole cells of Candida parapsilosis ATCC 7330. Tetrahedron Asymmetry 21(24):2973–2980

    Article  CAS  Google Scholar 

  26. Kaliaperumal T, Gummadi SN, Chadha A (2011) Candida parapsilosis ATCC 7330 can also deracemise 1-arylethanols. Biocatal Biotransformation 29(6):262–270

    CAS  Google Scholar 

  27. Baskar B, Pandian NG, Priya K, Chadha A (2004) Asymmetric reduction of alkyl 2-oxo-4-arylbutanoates and -but-3-enoates by Candida parapsilosis ATCC 7330: assignment of the absolute configuration of ethyl 2-hydroxy-4-(p-methylphenyl)but-3-enoate by 1H NMR. Tetrahedron Asymmetry 15(24):3961–3966

    Article  CAS  Google Scholar 

  28. Mahajabeen P, Chadha A (2011) One-pot synthesis of enantiomerically pure 1, 2-diols: asymmetric reduction of aromatic α-oxoaldehydes catalysed by Candida parapsilosis ATCC 7330. Tetrahedron Asymmetry 22 (24):2156–2160

  29. Stella S, Chadha A (2012) Biocatalytic reduction of α-keto amides to (R)-α-hydroxy amides using Candida parapsilosis ATCC 7330. Catal Today 198(1):345–352

    Article  CAS  Google Scholar 

  30. Kaliaperumal T, Kumar S, Gummadi S, Chadha A (2010) Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxybutanoate using Candida parapsilosis ATCC 7330. J Ind Microbiol Biotechnol 37(2):159–165

    Article  CAS  PubMed  Google Scholar 

  31. Venkataraman S, Roy R, Chadha A (2013) Asymmetric reduction of alkyl-3-oxobutanoates by Candida parapsilosis ATCC 7330: insights into solvent and substrate optimisation of the biocatalytic reaction. Appl Biochem Biotechnol 171(3):756–770

    Article  CAS  PubMed  Google Scholar 

  32. Allan GR, Carnell AJ (2001) Microbial deracemization of 1-aryl and 1-heteroaryl secondary alcohols. J Org Chem 66(19):6495–6497

    Article  CAS  PubMed  Google Scholar 

  33. Hasegawa J, Ogura M, Tsuda S, Maemoto S, Kutsuki H, Ohashi T (1990) High-yield production of optically active 1,2-diols from the corresponding racemates by microbial stereoinversion. Agric Biol Chem 54(7):1819–1827

    Article  CAS  Google Scholar 

  34. Matsuyama A, Yamamoto H, Kawada N, Kobayashi Y (2001) Industrial production of (R)-1,3-butanediol by new biocatalysts. J Mol Catal B Enzym 11(4–6):513–521

    Article  CAS  Google Scholar 

  35. Xie SX, Ogawa J, Shimizu S (1999) Production of (R)-3-pentyn-2-ol through stereoinversion of racemic 3-pentyn-2-ol by Nocardia fusca AKU 2123. Appl Microbiol Biotechnol 52(3):327–331

    Article  CAS  PubMed  Google Scholar 

  36. Xie SX, Ogawa J, Shimizu S (1999) NAD+-dependent (S)-Specific secondary alcohol dehydrogenase involved in stereoinversion of 3-pentyn-2-ol catalyzed by Nocardia fusca AKU 2123. Biosci Biotechnol Biochem 63(10):1721–1729

    Article  CAS  PubMed  Google Scholar 

  37. Balaji BS, Chanda BM (1998) Simple and high yielding syntheses of β-keto esters catalysed by zeolites. Tetrahedron 54(43):13237–13252

    Article  CAS  Google Scholar 

  38. Jin T, Zhang S, Li T (2002) Transesterification of β-ketoesters with alcohols catalyzed by montmorillonite K-10. Green Chem 4(1):32–34

    Article  CAS  Google Scholar 

  39. Padhi SK, Chadha A (2003) Sodium borohydride reduction and selective transesterification of β-keto esters in a one-pot reaction under mild conditions. Synlett 05:0639–0642

    Google Scholar 

  40. Nakamura K, Fujii M, Ida Y (2001) Stereoinversion of arylethanols by Geotrichum candidum. Tetrahedron Asymmetry 12(22):3147–3153

    Article  CAS  Google Scholar 

  41. Salvi NA, Chattopadhyay S (2004) Rhizopus arrhizus mediated asymmetric reduction of alkyl 3-oxobutanoates. Tetrahedron Asymmetry 15(21):3397–3400

    Article  CAS  Google Scholar 

  42. Mochizuki N, Sugai T, Ohta H (1994) Biochemical reduction of 3-oxoalkanoic esters by a bottom-fermentation yeast, Saccharomyces cerevisiae IFO 0565. Biosci Biotechnol Biochem 58(9):1666–1670

    Article  CAS  Google Scholar 

  43. Medson C, Smallridge AJ, Trewhella MA (1997) The stereoselective preparation of β-hydroxy esters using a yeast reduction in an organic solvent. Tetrahedron Asymmetry 8(7):1049–1054

    Article  CAS  Google Scholar 

  44. Griffin DR, Gainer JL, Carta G (2001) Asymmetric ketone reduction with immobilized yeast in hexane: biocatalyst deactivation and regeneration. Biotechnol Prog 17(2):304–310

    Article  CAS  PubMed  Google Scholar 

  45. Nakamura K, Matsuda T (1998) Asymmetric reduction of ketones by the acetone powder of Geotrichum candidum. J Org Chem 63(24):8957–8964

    Article  CAS  Google Scholar 

  46. Voss CV, Gruber CC, Kroutil W (2007) A biocatalytic one-pot oxidation/reduction sequence for the deracemisation of a sec-alcohol. Tetrahedron Asymmetry 18(2):276–281

    Article  CAS  Google Scholar 

  47. Thangavel V, Chadha A (2007) Preparation of optically pure (3E, 5E)-alkyl-2-hydroxy-6-arylhexa-3,5-dienoates by Candida parapsilosis ATCC 7330 mediated deracemisation of the racemates. Tetrahedron 63(19):4126–4133

    Article  CAS  Google Scholar 

  48. Keinan E, Hafeli EK, Seth KK, Lamed R (1986) Thermostable enzymes in organic synthesis. 2. Asymmetric reduction of ketones with alcohol dehydrogenase from Thermoanaerobium brockii. J Am Chem Soc 108(1):162–169

    Article  CAS  Google Scholar 

  49. Voss CV, Gruber CC, Kroutil W (2008) Deracemization of secondary alcohols through a concurrent tandem biocatalytic oxidation and reduction. Angew Chem Intl Ed 47(4):741–745

    Article  CAS  Google Scholar 

  50. Voss CV, Gruber CC, Faber K, Knaus T, Macheroux P, Kroutil W (2008) Orchestration of concurrent oxidation and reduction cycles for stereoinversion and deracemisation of sec-alcohols. J Am Chem Soc 130(42):13969–13972

    Article  CAS  PubMed  Google Scholar 

  51. Padhi SK, Titu D, Pandian NG, Chadha A (2006) Deracemisation of β-hydroxy esters using immobilised whole cells of Candida parapsilosis ATCC 7330: substrate specificity and mechanistic investigation. Tetrahedron 62(21):5133–5140

    Article  CAS  Google Scholar 

Download references

Acknowledgments

One of the authors (Sowmyalakshmi Venkataraman) gratefully acknowledges the Indian Institute of Technology (IIT) Madras, India for the fellowship. We thank the Sophisticated Analytical Instrumentation Facility (SAIF), IIT Madras for the NMR analysis.

Author information

Authors and Affiliations

  1. Laboratory of Bioorganic Chemistry, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600 036, India

    Sowmyalakshmi Venkataraman & Anju Chadha

  2. National Center for Catalysis Research, Indian Institute of Technology Madras, Chennai, 600 036, India

    Anju Chadha

Authors
  1. Sowmyalakshmi Venkataraman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anju Chadha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anju Chadha.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Venkataraman, S., Chadha, A. Biocatalytic deracemisation of aliphatic β-hydroxy esters: Improving the enantioselectivity by optimisation of reaction parameters. J Ind Microbiol Biotechnol 42, 173–180 (2015). https://doi.org/10.1007/s10295-014-1558-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-014-1558-5

Keywords

Search

Navigation