Skip to main content
SpringerLink
Log in

Efficient lipase-catalyzed Knoevenagel condensation: utilization of biocatalytic promiscuity for synthesis of benzylidene-indolin-2-ones

  • Original Paper
  • Published:
Bioprocess and Biosystems Engineering Aims and scope Submit manuscript

Abstract

Based on the screening of biocatalysts and reaction conditions including solvent, water content, temperature, enzyme loading, and reaction time, lipase from porcine pancreas (PPL) showed the prominent promiscuity for the Knoevenagel condensation between 1,3-dihydroindol-2-one heterocycle and aromatic aldehydes. Under the optimized procedure, both electron-withdrawing and electron-donating substituent of aldehydes substrates could react efficiently, and benzylidene-indolin-2-ones were obtained in excellent yields (75.0–96.6 %).

Graphical abstract

Benzylidene-indolin-2-ones derivatives were efficiently synthesized by the Knoevenagel condensation between various aromatic aldehydes and 1,3-dihydroindol-2-one catalyzed by lipase from porcine pancreas with excellent yields obtained.

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

Scheme 1
Fig. 1
Fig. 2
Scheme 2

Similar content being viewed by others

References

  1. Mukherjee R, Jaggi M, Rajendran P, Siddiqui MJA, Srivastava SK, Vardhan A, Burman AC (2004) Betulinic acid and its derivatives as anti- angiogenic agent. Bioorg Med Chem Lett 14:2181–2184

    Article  CAS  Google Scholar 

  2. Xu TT, Wang SY, Ji SJ (2006) Facile synthesis of Z/E-3-arylmethylidene-2,3-dihydro- indol-2-one under solvent-free conditions. Chin J Org Chem 26:1414–1417

    CAS  Google Scholar 

  3. Porcs-Makkay M, Volk B, Kapiller-Dezsofi R, Mezei T, Simig G (2004) New routes to oxindole derivatives. Monatsh Chem 135:697–711

    Article  CAS  Google Scholar 

  4. Du TP, Zhu GG, Zhou J (2012) A facile method for the synthesis of 3-alkyloxindole. Lett Org Chem 9:225–232

    Article  CAS  Google Scholar 

  5. Botta G, De Santis LP, Saladino R (2012) Current advances in the synthesis and antitumoral activity of SIRT1-2 inhibitors by modulation of p53 and pro-apoptotic proteins. Curr Med Chem 19:5871–5884

    Article  CAS  Google Scholar 

  6. Zhang W, Go ML (2009) Functionalized 3-benzylidene-indolin-2-ones: inducers of NAD(P)H-quinone oxidoreductase 1 (NQO1) with antiproliferative activity. Bioorg Med Chem 17:2077–2090

    Article  CAS  Google Scholar 

  7. Olgen S, Gotz C, Jose J (2007) Synthesis and biological evaluation of 3-(substituted-benzylidene)-1,3-dihydro-indolin derivatives as human protein kinase CK2 and p60(c-Src) tyrosine kinase inhibitors. Biol Pharm Bull 30:715–718

    Article  CAS  Google Scholar 

  8. Kuchar M, Steinbach J, Wuest F (2009) Synthesis and radiopharmacological investigation of 3-[4’-[F-18] fluorobenzylidene] indolin-2-one as possible tyrosine kinase inhibitor. Bioorg Med Chem 17:7732–7742

    Article  CAS  Google Scholar 

  9. Ding K, Wang GP, Deschamps JR, Parrish DA, Wang SM (2005) Synthesis of spirooxindoles via asymmetric 1,3-dipolar cycloaddition. Tetrahedron Lett 46:5949–5951

    Article  CAS  Google Scholar 

  10. Villemin D, Martin B (1998) Potassium fluoride on alumina: dry synthesis of 3-arylidene-1,3-dihydro-indol-2-one under microwave irradiation. Synth Commun 28:3201–3208

    Article  CAS  Google Scholar 

  11. Wang XS, Zeng ZS, Li YL, Shi DQ, Tu SJ, Wei XY, Zong ZM (2005) Synthesis of E-arylidene-2,3-dihydroindol-2-one derivatives in aqueous media catalyzed by triethylbenzylammonium chloride phase-transfer catalyst. Chin J Org Chem 25:1598–1601

    CAS  Google Scholar 

  12. Hu Y, Kang H, Zeng BW, Wei P, Huang H (2008) Facile synthesis of 3-arylidene-1,3-dihydroindol-2-ones catalysed by a Bronsted acidic ionic liquid. J Chem Res 11:642–643

    Article  Google Scholar 

  13. Friedrich S, Hahn F (2015) Opportunities for enzyme catalysis in natural product chemistry. Tetrahedron 71:1473–1508

    Article  CAS  Google Scholar 

  14. Reetz MT (2013) Biocatalysis in organic chemistry and biotechnology: past, present, and future. J Am Chem Soc 135:12480–12496

    Article  CAS  Google Scholar 

  15. Miao YF, Rahimi M, Geertsema EM, Poelarends GJ (2015) Recent developments in enzyme promiscuity for carbon-carbon bond-forming reactions. Curr Opin Chem Biol 25:115–123

    Article  CAS  Google Scholar 

  16. Kapoor M, Gupta MN (2012) Lipase promiscuity and its biochemical applications. Process Biochem 47:555–569

    Article  CAS  Google Scholar 

  17. Ding Y, Huang H, Hu Y (2013) New progress on lipases catalyzed C–C bond formation reactions. Chin J Org Chem 33:905–914

    Article  CAS  Google Scholar 

  18. Ding Y, Ni X, Gu MJ, Li S, Huang H, Hu Y (2015) Knoevenagel condensation of aromatic aldehydes with active methylene compounds catalyzed by lipoprotein lipase. Catal Commun 64:101–104

    Article  CAS  Google Scholar 

  19. Wang Z, Wang CY, Wang HR, Zhang H, Sun YL, Ji TF, Wang L (2014) Lipase-catalyzed Knoevenagel condensation between α, β-unsaturated aldehydes and active methylene compounds. Chin Chem Lett 25:802–804

    Article  CAS  Google Scholar 

  20. Jiang L, Yu HW (2014) Enzymatic promiscuity: Escherichia coli BioH esterase-catalysed Aldol reaction and Knoevenagel reaction. Chem Res Chin Univ 30:289–292

    Article  CAS  Google Scholar 

  21. Lai YF, Zheng H, Chai SJ, Zhang PF, Chen XZ (2010) Lipase-catalysed tandem Knoevenagel condensation and esterification with alcohol cosolvents. Green Chem 12:1917–1918

    Article  CAS  Google Scholar 

  22. Hu Y, Jiang XJ, Wu SW, Jiang L, Huang H (2013) Synthesis of vitamin E succinate by interfacial activated Candida rugosa lipase encapsulated in sol–gel materials. Chin J Catal 34:1608–1616

    Article  CAS  Google Scholar 

  23. Liu WM, Hu Y, Jiang L, Zou B, Huang H (2012) Synthesis of methyl (R)-3-(4-fluorophenyl)glutarate via enzymatic desymmetrization of a prochiral diester. Process Biochem 47:1037–1041

    Article  CAS  Google Scholar 

  24. Jiang XJ, Hu Y, Jiang L, Zou B, Huang H (2013) Optimization of enzymatic synthesis of l-ascorbyl palmitate by solvent engineering and statistical experimental designs. Biotechnol Bioproc Eng 18:350–357

    Article  CAS  Google Scholar 

  25. Laane C, Boeren S, Vos K, Veeger C (2009) Rules for optimization of biocatalysis in organic solvents. Biotechnol Bioeng 102:2–8

    Article  CAS  Google Scholar 

  26. Salihu A, Alam MZ (2015) Solvent tolerant lipases: a review. Process Biochem 50:86–96

    Article  CAS  Google Scholar 

  27. Doukyu N, Ogino H (2010) Organic solvent-tolerant enzymes. Biochem Eng J 48:270–282

    Article  CAS  Google Scholar 

  28. Hu W, Guan Z, Deng X, He YH (2012) Enzyme catalytic promiscuity: the papain-catalyzed Knoevenagel reaction. Biochimie 94:656–661

    Article  CAS  Google Scholar 

  29. Zaks A, Klibanov AM (1988) The effect of water on enzyme action in organic media. J Biol Chem 263:8017–8021

    CAS  Google Scholar 

  30. Narayan VS, Klibanov AM (1993) Are water-immiscibility and apolarity of the solvent relevant to enzyme efficiency? Biotechnol Bioeng 41:390–393

    Article  CAS  Google Scholar 

  31. Li K, He T, Li C, Feng XW, Wang N, Yu XQ (2009) Lipase-catalysed direct Mannich reaction in water: utilization of biocatalytic promiscuity for C–C bond formation in a “one-pot” synthesis. Green Chem 11:777–779

    Article  CAS  Google Scholar 

  32. Li C, Feng XW, Wang N, Zhou YJ, Yu XQ (2008) Biocatalytic promiscuity: the first lipase-catalysed asymmetric aldol reaction. Green Chem 10:616–618

    Article  CAS  Google Scholar 

  33. Sun FL, Xu G, Wu JP, Yang LR (2006) Efficient lipase-catalyzed kinetic resolution of 4-arylmethoxy-3-hydroxybutanenitriles: application to an expedient synthesis of a statin intermediate. Tetrahedron Asymmetry 17:2907–2913

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was financially supported by the Hi-Tech Research and Development Program of China (Grant No. 2011AA02A209) and National Science Foundation for Distinguished Young Scholars of China (Grant No. 21225626).

Author information

Authors and Affiliations

  1. State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 210009, People’s Republic of China

    Yan Ding, Xinran Xiang, Mengjie Gu, Haoran Xu, He Huang & Yi Hu

Authors
  1. Yan Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinran Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mengjie Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haoran Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. He Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to He Huang or Yi Hu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, Y., Xiang, X., Gu, M. et al. Efficient lipase-catalyzed Knoevenagel condensation: utilization of biocatalytic promiscuity for synthesis of benzylidene-indolin-2-ones. Bioprocess Biosyst Eng 39, 125–131 (2016). https://doi.org/10.1007/s00449-015-1496-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00449-015-1496-2

Keywords

Search

Navigation