Novel Bis-C,C-Glycosyl Derivatives: C-Glycosides of Heptulosonic Acids and Their Spirocyclization

Several bioactive natural and synthetic compounds bear spirocyclic units. Synthesis of this motif is still a great challenge, especially on a carbohydrate framework. Natural anomeric spirocyclic compounds such as the herbicide hydantocidin [1] and the papulacandins [2] with antifungal activity are well known, other synthetic compounds show glycosidase [3], glycogen phosphorylase [4] and SGLT2 inhibition [5]. A representative from the latter group has been marketed recently for the treatment of type 2 diabetes mellitus.

C-Glycosyl derivatives of ulosonic acids are scarcely known in the literature, such type of structures are limited only to the 3-deoxy type sialic acid derivatives. Herein we report a systematic study on the synthesis of bis-C,C-glycopyranosyl compounds from fully substituted heptulosonic acids followed by cyclization to novel spirocycles. From per-O-acylated (ulopyranosyl bromide)onic acid derivatives (1) further glycosyl donors (2) were prepared with various leaving groups and anomeric configurations and the ionic and radical reactions of 1 and 2 were investigated towards bis-C,C-glycosyl derivatives 3. Transformations of the anomeric C-substituents and cyclization steps led to spirocycles 4 with five and six membered heterorings.