Septanoses are unnatural carbohydrates, analogous to pyranoses. Septanoses have been evaluated as ligands of lectins and substrates for glycosidase enzymes, for example. Efficient methods for the preparation of septanoses are needed to accurately assess their usefulness in glycobiology. Oxepines, seven membered ring cyclic enol ethers, have been used as building blocks for synthesis of septanoses and natural products containing seven membered rings. Here we introduce an efficient seven-step method for the synthesis of carbohydrate based oxepines where reductive elimination of a septanosyl bromide is the key step in the synthesis. Since oxepines have similar reactivity profile to glycals, Fisher-Zack synthesis of glycals via reductive elimination of glycosylbromides was adapted to develop a simple and efficient seven-step route to oxepine synthesis. The synthesis starts with vinyl Grignard addition to the benzyl protected pyranoses, followed by ozonolysis to give hydroxyl aldehydes. Key intermediate peracetylseptanoses were prepared by diacetate formation of hydroxyl aldehyde followed by debenzylation and acetylation sequence. The efficiency and economy of this method made it amenable to gram scale synthesis of various substituted oxepines.

Practical, scalable synthesis of carbohydrate based oxepines

249th National Meeting (2015)

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