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Stereoselective Synthesis of Iminosugar-C-Glycosides through Addition of Organometallic Reagents to N-tert-Butanesulfinyl Glycosylamines: A Comprehensive Study |
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| Authors: | Daniel Kamzol Maxime Neuville Chloé Cocaud Killian Tiger Baptiste Taffoureau Prof. Dr. Krzysztof Lewiński Justyna Jaszczyk Prof. Dr. Olivier R. Martin Dr. Sebastian Baś Prof. Dr. Sylvain Routier Prof. Dr. Isabelle Gillaizeau Dr. Frédéric Buron Dr. Cyril Nicolas |
| Affiliation: | 1. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France Contribution: Formal analysis (lead), Investigation (lead);2. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal);3. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal);4. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France Contribution: Formal analysis (supporting), Investigation (equal);5. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France Contribution: Investigation (supporting);6. Faculty of Chemistry, Department of Crystal Chemistry and Crystal Physics, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland Contribution: Data curation (lead), Formal analysis (lead), Investigation (lead), Writing - original draft (supporting);7. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France Contribution: Funding acquisition (equal), Writing - original draft (supporting);8. Faculty of Chemistry, Department of chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland Contribution: Supervision (supporting), Writing - original draft (supporting);9. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France Contribution: Funding acquisition (equal);10. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France Contribution: Funding acquisition (lead), Writing - original draft (supporting);11. Institut de Chimie Organique et Analytique, UMR CNRS 7311, Université d'Orléans, Rue de Chartres – BP 6759, 45067 Orléans Cedex 2, France |
| Abstract: | A comprehensive study of the preparation and reactivity of N-tert-butanesulfinyl glycosylamines with simple Grignard and organo lithium reagents in batch vs. continuous flow chemistry is reported. As they readily react as latent imine equivalents with a variety of carbon nucleophiles, these carbohydrate derivatives constitute very useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar-C-glycosides. A hybrid protocol, involving the addition of benzylmagnesium chloride to a (SR)-arabinofuranosylamine substrate in flow, at room temperature, combined with a cyclization protocol in batch is also described for the first time. Of note, this semi-continuous flow process shortens the synthesis of imino-C-glycoside scaffolds to a single workday. |
| Keywords: | N-tert-butanesulfinyl glycosylamines Grignard addition organolithium addition stereoselective synthesis flow chemistry iminosugar-C-glycosides |