CARB 78 |
| The stereoselective synthesis of a β-D-mannopyranoside bond is one of the most difficult linkages to achieve due to steric repulsion from the C2 axial group and the anomeric effect. Recent literature offers numerous developments in the synthesis of β- mannoside linkages. Among these efforts, Paulsen introduced the use of insoluble silver salts to aid in the replacement of the α-anomeric bromide with inversion to the corresponding β-mannoside. More recently Crich and Sun controlled the β-selectivity based on sulfoxide glycosylation and benzylidene conformational effects. Despite all the efforts in literature no one strategy seems to be universal for the synthesis of β- mannoside linkages. Inspired by the reactivity of glycosyl iodides and the fact that the formed glycosides are often stereoselective, we were encouraged to investigate their use in the stereoselective synthesis of β-mannosides. The reaction reported herein involves the use of mannosyl iodide as the donor and trimethylene oxide as the acceptor. It proceeds in high yield and forms the product with over 90% β-selectivity, which is believed to arise from direct displacement of the α-iodide. Excess iodide during the course of the reaction participates in in situ anomerization of the α-anomeric iodide to the β-analogue, which if attacked produces the undesired α-glycoside. Thus methods for inhibiting or limiting in situ anomerization are required to drive the reaction mechanism to the formation of the β-glycoside. Herein we report two simple but efficient methods that fulfill this purpose. |
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General Papers: Synthesis of Carbohydrates and Derivatives
1:30 PM-5:10 PM, Wednesday, 29 March 2006 Georgia World Congress Center -- B409, Oral
Division of Carbohydrate Chemistry |