Experimental design of the kinetic resolution of a key precursor of high-value bioactive myo-inositols by an immobilized lipase

Authors

  • Aline G. Cunha,

    Corresponding author
    1. UFRJ, Instituto de Química, CT, Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
      Aline G. Cunha and Denise M. G. Freire, UFRJ, Instituto de Química, CT, Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Ilha do Fundão, Rio de Janeiro, RJ, Brazil. E-mail: alinegc_iq@yahoo.com.br; freire@iq.ufrj.br
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  • Angelo A. T. da Silva,

    1. UFRJ, Núcleo de Pesquisas de Produtos Naturais (NPPN), CCS, bloco H, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
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  • Mateus G. Godoy,

    1. UFRJ, Instituto de Química, CT, Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
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  • Rodrigo V. Almeida,

    1. UFRJ, Instituto de Química, CT, Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
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  • Alessandro B. C. Simas,

    1. UFRJ, Núcleo de Pesquisas de Produtos Naturais (NPPN), CCS, bloco H, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
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  • Denise M. G. Freire

    Corresponding author
    1. UFRJ, Instituto de Química, CT, Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Ilha do Fundão, Rio de Janeiro, RJ, Brazil
      Aline G. Cunha and Denise M. G. Freire, UFRJ, Instituto de Química, CT, Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Ilha do Fundão, Rio de Janeiro, RJ, Brazil. E-mail: alinegc_iq@yahoo.com.br; freire@iq.ufrj.br
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Aline G. Cunha and Denise M. G. Freire, UFRJ, Instituto de Química, CT, Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Ilha do Fundão, Rio de Janeiro, RJ, Brazil. E-mail: alinegc_iq@yahoo.com.br; freire@iq.ufrj.br

Abstract

BACKGROUND: The response surface methodology was successfully applied to the optimization of the reaction variables for the kinetic resolution of a precursor of high-value myo-inositols, ( ± )-1,2-O-isopropylidene-3,6-di-O-benzyl-myo-inositol (( ± )-1), by Novozym 435. The resolutions were run separately, with two acylating agents, ethyl acetate and vinyl acetate, in a solvent-free system. The variables analyzed were reaction temperature, substrate concentration, water concentration and enzyme activity. A statistical model was employed for the evaluation of the influence of the variables on conversion and enantiomeric excess (ee).

RESULTS: The optimal conditions for this resolution using vinyl acetate as acylating agent were 45 °C, 5 mg mL−1 of substrate, 71 U of enzyme activity and 0%w/w of water concentration. The high conversion (49.2 %) and ee (>99%) reached in the chemoenzymatic synthesis of acylated product, L-(−)-5-O-Acetyl-3,6-di-O-benzyl-1,2-O-isopropylidene-myo-inositol, secure the efficient synthesis of the D enantiomorph present in the original racemic mixture (( ± )-1) as well.

CONCLUSIONS: The use of the experimental design strategy was productive, leading to a 14-fold increase in the productivity of the reaction compared with the non-optimized conditions. Both derivative L-(−)-2 and remaining substrate D-(+)-1 were obtained at high ee. © 2012 Society of Chemical Industry

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