Synthesis of Methylene Tetrahydrofurane-Fused Carbohydrates

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 regioselective 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.

Automated summary

A reliable method for introducing a fused methylene tetrahydrofuran ring into carbohydrates is disclosed. The resulting bicyclic saccharides can serve as scaffolds in medicinal chemistry and drug design. Furthermore, the enol ether functionality allows for modification in biological systems via photoclick chemistry. The method involves the regioselective oxidation of the C-3 hydroxy group in gluco-configured pyranosides, followed by stereoselective indium-mediated allylation. The formation of the ring is induced by an iodocyclization reaction with a neighboring hydroxy group, and subsequent dehydrohalogenation produces the desired methylene-tetrahydrofuran-containing carbohydrates.