Article
Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors
Author/s | Fuente, Alex de la
Mena Barragán, Teresa Farrar-Tobar, Ronald A. Verdaguer, Xavier García Fernández, José Manuel Ortiz Mellet, Carmen Riera, Antoni |
Department | Universidad de Sevilla. Departamento de Química orgánica |
Publication Date | 2015 |
Deposit Date | 2017-09-12 |
Published in |
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Abstract | 2-Acetamido-1,2-dideoxyiminosugars are selective and potent inhibitors of hexosaminidases and therefore show high therapeutic potential for the treatment of various diseases, including several lysosomal storage disorders. ... 2-Acetamido-1,2-dideoxyiminosugars are selective and potent inhibitors of hexosaminidases and therefore show high therapeutic potential for the treatment of various diseases, including several lysosomal storage disorders. A stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc), the iminosugar analog of N-acetylglucosamine, with a high overall yield is here described. This novel procedure further allowed accessing ureido-DNJNAc conjugates through derivatization of the endocyclic amine on a key pivotal intermediate. Remarkably, some of the ureido-DNJNAc representatives behaved as potent and selective inhibitors of β-hexosaminidases, including the human enzyme, being the first examples of neutral sp2-iminosugar-type inhibitors reported for these enzymes. Moreover, the amphiphilic character of the new ureido-DNJNAc is expected to confer better drug-like properties. |
Project ID. | info:eu-repo/grantAgreement/MINECO/CTQ2011-23620
info:eu-repo/grantAgreement/MINECO/SAF2013-44021R info:eu-repo/grantAgreement/MINECO/CTQ2010-15848 2014SGR 234 FQM-1467 |
Citation | Fuente, A.d.l., Mena Barragán, T., Farrar-Tobar, R.A., Verdaguer, X., García Fernández, J.M., Ortiz Mellet, C. y Riera, A. (2015). Stereoselective synthesis of 2-acetamido-1,2-dideoxynojirimycin (DNJNAc) and ureido-DNJNAc derivatives as new hexosaminidase inhibitors. Organic and Biomolecular Chemistry, 13, 6500-6510. |
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