Synthesis of Methylene Tetrahydrofurane‐Fused Carbohydrates

Abstract

A reliable method is disclosed to introduce a fused methylene tetrahydrofuran ring into carbohydrates. The resulting bicyclic saccharides can be used as scaffolds in medicinal chemistry and drug design. In addition, the enol ether functionality serves as a handle that enables modification in biological systems via photoclick chemistry. The approach is based on the regioselec-tive oxidation of the C-3 hydroxy group in gluco-configured pyranosides, followed by stereoselective indium-mediated allylation. The ring formation is induced by an iodocyclization reaction with a neighboring hydroxy group. Subsequent dehydrohalogenation affords the desired methylene-tetrahydrofuran-containing carbohydrates.

Practical Site-selective Oxidation of Glycosides with Pd(OAc)2/Neocuproine

“…Our group has exploited the keto functionality of unprotected ketosaccharides in the synthesis of rare sugars 27 and, in further modifications, to allow their use in chemical biology, for example, through the introduction of an allyl or an alkyne handle, exocyclic and endocyclic epoxides, an amine or a chloride, and recently, a thiol moiety. [28][29][30][31] Despite all these illustrations of the versatility and applicability of Waymouth's catalyst in carbohydrate oxidation, its incorporation in the toolbox of the carbohydrate chemist has been slow. The main reason is probably that the catalyst is not commercially available and has to be prepared.…”

“…Our group has exploited the keto functionality of unprotected ketosaccharides in the synthesis of rare sugars 27 and, in further modifications, to allow their use in chemical biology, for example, through the introduction of an allyl or an alkyne handle, exocyclic and endocyclic epoxides, an amine or a chloride, and recently, a thiol moiety. 28 29 30 31…”