New route to C-glycoside creation overcomes earlier drawbacks

A one-pot process for creating C-glycosides could help prepare robust analogues of naturally occurring carbohydrates, report chemists who developed the process. The technique could ultimately be used to make carbohydrate derivatives more widely available for use in applications from drugs to biosensors. 

Naturally occurring sugar molecules are linked by an O-acetal bond, which is highly susceptible to hydrolysis. A more stable linkage would be to replace acetal oxygen with a carbon group. But conventional methods of doing this require complex, multi-step chemistry in which exposed hydroxyl groups on the sugar ring need to be capped by protecting groups, and then restored at the end of the process. 

Now, groups led by Richard Taylor at the University of York, UK, and Richard Franck at Hunter College, US, have devised a sulfur-based route to C-glycoside creation.   Taylor’s group has extended the procedure to develop a one-pot process that does not require protection of OH groups.

The UK researchers reacted 2-deoxy-D-ribose, which has three OH groups, with a sulfonyl Wittig reagent, which specifically attacks only the anomeric carbon of the sugar, replacing its OH with a CH₂SO₂R group. This sulfone is then subjected to the Ramberg-B?cklund reaction, in which it is exposed to a base and a halogenating agent, resulting in the sulfone group being replaced by a double-bonded carbon to create the C-glycoside.

Paul Murphy from University College Dublin, Ireland, is interested in the synthesis of bioactive carbohydrate derivatives. ’This approach is very attractive because one can envisage the synthesis of a wide variety of novel C-glycoconjugates of biological relevance without the need to manipulate protecting groups, which can cause difficulties,’ Murphy told Chemistry World.

Simon Hadlington