Directing-protecting groups for carbohydrates. Design, conformational study, synthesis and application to regioselective functionalization |
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Authors: | Nicolas Moitessier Pablo Englebienne |
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Institution: | a Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montréal, Québec, Canada H3A 2K6 b Groupe SUCRES, Unité Mixte 7565 CNRS, Université Henri Poincaré-Nancy 1, B.P. 239, F-54506 Nancy-Vandoeuvre, France |
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Abstract: | A novel concept of regioselective transformation of secondary hydroxyl groups in carbohydrates is presented. First, the relative reactivity of the free hydroxyl groups of onoprotected d-glucose derivatives was assessed using acetylation as a model reaction. As a result, acylation of these polyols gave a mixture of monosubstituted products in which the 3-O functionalized derivatives predominated. Novel hydrogen bond acceptor protecting groups were next designed to modulate the 4-OH and 3-OH reactivity in the hope to mediate higher regioselective transformations. A molecular modeling study later validated by spectroscopic analysis predicted additional intramolecular hydrogen bonds between the hydroxyl groups and pyridyl-containing protecting groups. Taking advantage of this induced hydrogen bond network, we achieved regioselective acetylation of the hydroxyl group at position 3 without protecting any secondary hydroxyl groups of the carbohydrate moiety. This designed protecting/directing group increased the nucleophilicity and the steric hindrance of position 3. As a result, optimization of the reaction conditions enabled the monoacetylation (not affected by steric hindrance) of 6-O-protected glucopyranosides at position 3 and selective silylation (affected by steric hindrance) of position 2 in high isolated yields and regioselectivities. This result certainly opens doors to the regioselective open glycosylation of carbohydrates. |
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Keywords: | Carbohydrate Relative reactivity Regioselectivity Open glycosylation Hydrogen bond Pyridyl ring Acetylation |
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