A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 Scaffold
A straightforward synthetic route towards DAB-1 scaffolded dimeric iminosugars is described here, starting from readily available bis-glycosylamines. The method allows the integration of a variety of linkages (aryl, alkyl, polyethyleneglycol chains) between both iminosugars through the choice of the...
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2025-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/2/226 |
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| author | Kamilia Ould Lamara Nathan Noël Fabien Massicot Jean-Luc Vasse Stéphane P. Vincent Jean-Bernard Behr |
| author_facet | Kamilia Ould Lamara Nathan Noël Fabien Massicot Jean-Luc Vasse Stéphane P. Vincent Jean-Bernard Behr |
| author_sort | Kamilia Ould Lamara |
| collection | DOAJ |
| description | A straightforward synthetic route towards DAB-1 scaffolded dimeric iminosugars is described here, starting from readily available bis-glycosylamines. The method allows the integration of a variety of linkages (aryl, alkyl, polyethyleneglycol chains) between both iminosugars through the choice of the bis-amine used in the first step. Moreover, an additional substituent (allyl, ethynyl) may be inserted into the structure via nucleophilic addition of an organometallic reagent to the starting bis-glycosylamine. A symmetrical ethynyl-iminosugar proved susceptible to intramolecular Glaser coupling, affording the corresponding macrocyclic structure. Dimeric iminosugars were tested towards a series of commercial glycosidases to uncover potencies and selectivities when compared to DAB-1, their monomeric counterpart. Whereas a significant drop in inhibition potencies was observed towards glucosidases, some compounds displayed unexpected potent inhibition of β-galactosidase. |
| format | Article |
| id | doaj-art-4d3135b1405246da86315f6c487247d5 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-4d3135b1405246da86315f6c487247d52025-01-24T13:43:10ZengMDPI AGMolecules1420-30492025-01-0130222610.3390/molecules30020226A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 ScaffoldKamilia Ould Lamara0Nathan Noël1Fabien Massicot2Jean-Luc Vasse3Stéphane P. Vincent4Jean-Bernard Behr5Université de Reims Champagne-Ardenne, CNRS, ICMR, 51097 Reims, FranceUniversité de Reims Champagne-Ardenne, CNRS, ICMR, 51097 Reims, FranceUniversité de Reims Champagne-Ardenne, CNRS, ICMR, 51097 Reims, FranceUniversité de Reims Champagne-Ardenne, CNRS, ICMR, 51097 Reims, FranceNARILIS (Namur Research Institute for Life Sciences), UNamur, Rue de Bruxelles 61, 5000 Namur, BelgiumUniversité de Reims Champagne-Ardenne, CNRS, ICMR, 51097 Reims, FranceA straightforward synthetic route towards DAB-1 scaffolded dimeric iminosugars is described here, starting from readily available bis-glycosylamines. The method allows the integration of a variety of linkages (aryl, alkyl, polyethyleneglycol chains) between both iminosugars through the choice of the bis-amine used in the first step. Moreover, an additional substituent (allyl, ethynyl) may be inserted into the structure via nucleophilic addition of an organometallic reagent to the starting bis-glycosylamine. A symmetrical ethynyl-iminosugar proved susceptible to intramolecular Glaser coupling, affording the corresponding macrocyclic structure. Dimeric iminosugars were tested towards a series of commercial glycosidases to uncover potencies and selectivities when compared to DAB-1, their monomeric counterpart. Whereas a significant drop in inhibition potencies was observed towards glucosidases, some compounds displayed unexpected potent inhibition of β-galactosidase.https://www.mdpi.com/1420-3049/30/2/226iminosugarsmultivalencyglycosylaminesglycosidasesinhibitionglycophanes |
| spellingShingle | Kamilia Ould Lamara Nathan Noël Fabien Massicot Jean-Luc Vasse Stéphane P. Vincent Jean-Bernard Behr A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 Scaffold Molecules iminosugars multivalency glycosylamines glycosidases inhibition glycophanes |
| title | A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 Scaffold |
| title_full | A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 Scaffold |
| title_fullStr | A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 Scaffold |
| title_full_unstemmed | A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 Scaffold |
| title_short | A Bis-Glycosylamine Strategy for the Synthesis of Dimeric Iminosugars Based on a DAB-1 Scaffold |
| title_sort | bis glycosylamine strategy for the synthesis of dimeric iminosugars based on a dab 1 scaffold |
| topic | iminosugars multivalency glycosylamines glycosidases inhibition glycophanes |
| url | https://www.mdpi.com/1420-3049/30/2/226 |
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