Ring-Opening of Benzylated Gluconolactone to Access Useful Gluconamide Conjugates

The formation of an amide linkage between carbohydrates at oxidized C-1 position and amines represent a useful transformation for the preparation of glycoconjugates. The aldonamides thus formed can be further functionalized to generate medically relevant tools, such as glucosidase inhibitors, ¹ acetylhexosaminidase inhibitors, ² sodium-glucose co-transporter-2 (SGLT2) inhibitors, ³ ice recrystallization inhibitors, ⁴ and intermediates for the preparation of aza-and l-sugars. ⁵ Methods used to generate amide conjugates rely on ring-opening of sugar-derived lactones without protecting groups. Purification of polar aldonamines provides the desired compound in low yield ⁶ or requires protection of the hydroxyl groups. ⁷ The use of toxic or expensive Lewis acids is also common for this transformation. ^5a,b,8 Other methods known to generate such compounds include oxidative amidation of aldoses ⁹ and the use of a lactone opening/silyl protection/amide coupling protocol. ¹⁰ Although these methods represent useful synthetic alternatives, low yield or long synthetic sequences are major drawbacks.