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

PS1 Poster session 1 Odd numbers
Location (hall): 
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Monday, July 1, 2019 - 15:45 to 17:15

Sándor Kun1, Nándor Kánya1, Nóra Magos1, László Somsák1

1Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary

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.

Figure 1. Synthesis and spirocyclization of bis-C,C-glycosyl derivatives

  1. Soengas, R. G.; Da Silva, G.; Estévez, J. C. Synthesis of Spironucleosides: Past and Future Perspectives. Molecules 2017, 22, 2028.
  2. Kobayashi, T.; Regens, C. S.; Denmark, S. E. In Strategies and Tactics in Organic Synthesis, Harmata, M., Ed. Academic Press: 2012, 8, 79-126.
  3. Tite, T.; Tomas, L.; Docsa, T.; Gergely, P.; Kovensky, J.; Gueyrard, D.; Wadouachi, A. Synthesis of N-aryl spiro-sulfamides as potential glycogen phosphorylase inhibitors. Tetrahedron Lett. 2012, 53, 959-961.
  4. Somsák, L. Glucose derived inhibitors of glycogen phosphorylase. Compt. Rend. Chimie 2011, 14, 211-223.
  5. Aguillón, A. R.; Mascarello, A.; Segretti, N. D.; de Azevedo, H. F. Z.; Guimaraes, C. R. W.; Miranda, L. S. M.; de Souza, R. O. M. A. Synthetic Strategies toward SGLT2 Inhibitors. Organic Process Research & Development 2018, 22, 467-488.