Rapid synthesis of propyl caffeate in ionic liquid using a packed bed enzyme microreactor under continuous-flow conditions.

Propyl caffeate has the highest antioxidant activity among caffeic acid alkyl esters, but its industrial production via enzymatic transesterification in batch reactors is hindered by a long reaction time (24h). To develop a rapid process for the production of propyl caffeate in high yield, a continuous-flow microreactor composed of a two-piece PDMS in a sandwich-like microchannel structure was designed for the transesterification of methyl caffeate and 1-propanol catalyzed by Novozym 435 in [B mim][CF3SO3]. The maximum yield (99.5%) in the microreactor was achieved in a short period of time (2.5h) with a flow rate of 2 μL/min, which kinetic constant Km was 16 times lower than that of a batch reactor. The results indicated that the use of a continuous-flow packed bed enzyme microreactor is an efficient method of producing propyl caffeate with an overall yield of 84.0%.

[1]  Fuan Wu,et al.  Pentyl (E)-3-(3,4-dihydroxyphenyl)acrylate , 2011, Acta crystallographica. Section E, Structure reports online.

[2]  F. Shahidi,et al.  A novel chemoenzymatic synthesis of phytosteryl caffeates and assessment of their antioxidant activity , 2012 .

[3]  G. Feijoo,et al.  Improving the catalytic performance of laccase using a novel continuous-flow microreactor , 2013 .

[4]  Liang Yu,et al.  Enhancement of the selective enzymatic biotransformation of rutin to isoquercitrin using an ionic liquid as a co-solvent. , 2013, Bioresource technology.

[5]  Chulhwan Park,et al.  β-Galactosidase-immobilised microreactor fabricated using a novel technique for enzyme immobilisation and its application for continuous synthesis of lactulose , 2012 .

[6]  R. Yunes,et al.  Antinociceptive properties of caffeic acid derivatives in mice. , 2009, European journal of medicinal chemistry.

[7]  Na Pang,et al.  Lipase-Catalyzed Synthesis of Caffeic Acid Propyl Ester in Ionic Liquid , 2013 .

[8]  Mitsuhiro Takeshita,et al.  Inhibitory effect of the alkyl side chain of caffeic acid analogues on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages. , 2008, Bioorganic & medicinal chemistry.

[9]  R. Schiffelers,et al.  Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes. , 2011, International journal of pharmaceutics.

[10]  D. Wei,et al.  Carica papaya lipase-catalyzed synthesis of terpene esters , 2011 .

[11]  Polona Žnidaršič-Plazl,et al.  Lipase-catalyzed synthesis of isoamyl acetate in an ionic liquid/n-heptane two-phase system at the microreactor scale. , 2009, Lab on a chip.

[12]  Patrick L. Mills,et al.  Microreactor technology and process miniaturization for catalytic reactions—A perspective on recent developments and emerging technologies , 2007 .

[13]  V. Freire,et al.  The new flow system approach in packed bed reactor applicable for immobilized enzyme , 2012 .

[14]  L. Vergnes,et al.  Effect of ethyl esterification of phenolic acids on low-density lipoprotein oxidation. , 2001, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[15]  H. J. Heeres,et al.  Kinetic studies on the Rhizomucor miehei lipase catalyzed esterification reaction of oleic acid with 1-butanol in a biphasic system , 2008 .

[16]  Dirk Weuster-Botz,et al.  Recycling of the ionic liquid phase in process integrated biphasic whole-cell biocatalysis , 2011 .

[17]  Fuan Wu,et al.  A novel chemoenzymatic synthesis of propyl caffeate using lipase-catalyzed transesterification in ionic liquid. , 2013, Bioresource technology.

[18]  M. Cordeiro,et al.  Phenolic acid derivatives with potential anticancer properties--a structure-activity relationship study. Part 1: methyl, propyl and octyl esters of caffeic and gallic acids. , 2004, Bioorganic & medicinal chemistry.

[19]  D. Maurya,et al.  Antioxidant and prooxidant nature of hydroxycinnamic acid derivatives ferulic and caffeic acids. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[20]  D. Desai,et al.  Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth. , 1992, Chemico-biological interactions.

[21]  Sang Hyun Lee,et al.  Effect of ionic liquids on enzymatic synthesis of caffeic acid phenethyl ester , 2011, Bioprocess and Biosystems Engineering.

[22]  G. Fieg,et al.  Experiment based model development for the enzymatic hydrolysis in a packed-bed reactor with biphasic reactant flow , 2011 .

[23]  P. Su,et al.  Online immobilized enzyme microreactor for the glucose oxidase enzymolysis and enzyme inhibition assay. , 2012, Analytical biochemistry.

[24]  J. Yoshida,et al.  Reactions of organolithiums with dialkyl oxalates. A flow microreactor approach to synthesis of functionalized α-keto esters. , 2013, Chemical communications.

[25]  Fuan Wu,et al.  A study of esterification of caffeic acid with methanol using p-toluenesulfonic acid as a catalyst , 2013 .

[26]  Polona Žnidaršič-Plazl,et al.  Integrated system of a microbioreactor and a miniaturized continuous separator for enzyme catalyzed reactions , 2012 .

[27]  Polona Žnidaršič-Plazl,et al.  Isoamyl acetate synthesis in imidazolium-based ionic liquids using packed bed enzyme microreactor , 2012 .

[28]  Pedro Fernandes,et al.  Microfluidic Devices: Useful Tools for Bioprocess Intensification , 2011, Molecules.

[29]  G. M. Greenway,et al.  Enzymatic synthesis of a series of alkyl esters using novozyme 435 in a packed-bed, miniaturized, continuous flow reactor , 2008 .

[30]  Peter H Seeberger,et al.  Continuous-flow synthesis of the anti-malaria drug artemisinin. , 2012, Angewandte Chemie.

[31]  Fuan Wu,et al.  Lipase-catalyzed Synthesis of Caffeic Acid Phenethyl Ester in Ionic Liquids: Effect of Specific Ions and Reaction Parameters , 2013 .

[32]  T. Fujita,et al.  Synthesis of 3-cyclohexylpropyl caffeate from 5-caffeoylquinic acid with consecutive enzymatic conversions in ionic liquid , 2011 .

[33]  S. Matsumoto,et al.  Direct synthesis of hydrogen peroxide based on microreactor technology , 2013 .

[34]  I. Gülçin.  Antioxidant activity of caffeic acid (3,4-dihydroxycinnamic acid). , 2006, Toxicology.

[35]  Oscar Ces,et al.  Design of a prototype flow microreactor for synthetic biology in vitro. , 2013, Lab on a chip.