Making Glucosepane In Eight Steps

Some proteins are known to react with the open-chain forms of carbohydrates, forming adducts that have been linked to diabetes, inflammation, and aging. When this reaction happens between proteins and glucose, the moiety formed is called glucosepane. Scientists think there’s a direct relationship between glucosepane and symptoms of diabetes. But studying glucosepane has proven problematic because it’s difficult to isolate the adduct from biological samples and the glucosepane exists naturally as a mix of eight diastereomers. Thanks to a concise enantioselective synthesis devised by Yale University chemists David A. Spiegel, Cristian Draghici, and Tina Wang, scientists can now make and study all of these glucosepane isomers (Science 2015, DOI: 10.1126/science.aac9655). The key step in the eight-step synthesis is a one-pot procedure for making the nonaromatic 4H-imidazole tautomer. Because the synthesis is short and modular, the Yale chemists believe it will find many applications. For example, the synthesis could be used to incorporate glucosepane into synthetic oligopeptides, or it could help identify novel therapies for breaking glucosepane cross-links.