Get access
Advertisement

Total Syntheses of Casuarine and Its 6-O-α-Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families

Authors

  • Francesca Cardona Dr.,

    1. Department of Organic Chemistry “U. Schiff”, Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), University of Florence, Via della Lastruccia, 13, 50019 Sesto Fiorentino (FI) (Italy), Fax: (+39) 055-457-3531
    Search for more papers by this author
  • Camilla Parmeggiani,

    1. Department of Organic Chemistry “U. Schiff”, Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), University of Florence, Via della Lastruccia, 13, 50019 Sesto Fiorentino (FI) (Italy), Fax: (+39) 055-457-3531
    Search for more papers by this author
  • Enrico Faggi Dr.,

    1. Department of Organic Chemistry “U. Schiff”, Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), University of Florence, Via della Lastruccia, 13, 50019 Sesto Fiorentino (FI) (Italy), Fax: (+39) 055-457-3531
    Search for more papers by this author
  • Claudia Bonaccini Dr.,

    1. Laboratory of Molecular Modeling, Cheminformatics & QSAR, Department of Pharmaceutical Sciences, Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino (FI) (Italy)
    Search for more papers by this author
  • Paola Gratteri Prof.,

    1. Laboratory of Molecular Modeling, Cheminformatics & QSAR, Department of Pharmaceutical Sciences, Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino (FI) (Italy)
    Search for more papers by this author
  • Lyann Sim,

    1. Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 101 College St., Toronto M5G 1L7 (Canada)
    Search for more papers by this author
  • Tracey M. Gloster Dr.,

    1. York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York, YO10 5YW (UK)
    Search for more papers by this author
  • Shirley Roberts,

    1. York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York, YO10 5YW (UK)
    Search for more papers by this author
  • Gideon J. Davies Prof.,

    1. York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York, YO10 5YW (UK)
    Search for more papers by this author
  • David R. Rose Prof.,

    1. Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 101 College St., Toronto M5G 1L7 (Canada)
    Search for more papers by this author
  • Andrea Goti Prof.

    1. Department of Organic Chemistry “U. Schiff”, Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles (HeteroBioLab), University of Florence, Via della Lastruccia, 13, 50019 Sesto Fiorentino (FI) (Italy), Fax: (+39) 055-457-3531
    Search for more papers by this author

Abstract

Selective glucosylation: Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-α-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao–Fleming oxidation and selective α-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes.

original image

Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-α-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao–Fleming oxidation and selective α-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.

Get access to the full text of this article

Ancillary