Stereochemical study of chemical glycosylation with c-3 and c-4 deoxofluorinated 2-azido-2-deoxy-hexopyranosyl donors

Session: 
S6.3 Glycosylation mechanisms and strategies
Code: 
OL6.3.2
Location (hall): 
Galactose
Start/end time: 
Tuesday, July 2, 2019 - 17:30 to 17:45
Martin
Kurfirt

Martin Kurfirt1, Jindřich  Karban1, Lucie Červenková-Šťastná1, Martin Dračíský2

1Institute of Chemical Process Fundamentals of the CAS, v. v. i., Prague, Czech Republic, 2Institute of Organic Chemistry and Biochemistry of the CAS, Prague, Czech Republic

Aminosugars are appreciably abundant in nature. They play crucial roles in many essential biological events. Derivatives of αand βlinked D-glucosamine and D-galactosamine represent typical carbohydrate structures occurring in glycoconjugates on the cell surface and in the extracellular matrix. These aminosugars participate in processes like tumor metastasis or immune response which are currently intensively studied [1].  Research into these processes necessitates carbohydrate derivatives including appropriate carbohydrate mimics. Fluorinated sugars seem to be suitable for this purpose. A replacement of a hydroxyl group by fluorine (deoxofluorination) represents an established and often very useful way to modulate chemical as well as biological properties of the parent carbohydrates. Deoxofluorinated sugars often successfully mimic natural carbohydrates due to similarities between oxygen and fluorine. This makes them very promising compounds for studying carbohydrate-protein recognition processes by advanced ¹⁹F-NMR epitope mapping techniques [2]. 

The synthesis of oligosaccharides and glycoconjugates containing fluorinated analogs of D-glucosamine and D-galactosamine requires a preparation of deoxofluorinated 2-amino-2-deoxyhexopyranosyl donors end examination of their reactivity. Corresponding donors were prepared from 3-fluoro or 4-fluoro 1,6-anhydro-2-azido-2-deoxy-D-gluco- and galactopyranoses. Preactivation protocol utilizing diphenyl sulfoxide/triflic anhydride (Ph₂SO/Tf₂O) [3] was used and the results obtained by glycosylation of common model carbohydrate acceptors [4] will be presented. A preparation of multivalent deoxofluorinated glycoclusters employing the results obtained in the model glycosylations will be also presented and a discussion of stereoselectivity based on a computation study of the proposed reaction intermediates will be included.

Fig.1 - Important results of the glycosylation stereoselectivity study.

References: 
  1. Fuster, M. M.; Esko, J. D. Nat. Rev. Cancer 2005, 5, 526–542.
  2. Diercks, T.; Infantino, A. S.; Unione, L.; Jiménez-Barbero, J.; Oscarson, S.; Gabius, H. J. Chem. Eur. J. 2018, 24, 15761–15765.
  3. Codée, J. D. C.; Litjens, R. E. J. N.; den Heeten, R.; Overkleeft, H. S.; van Boom, J. H.; van der Marel, G. A. Org. Lett. 2003, 5, 1519–1522.
  4. van der Vorm, S.; Overkleeft, H. S.; van der Marel, G. A.; Codée, J. D. C. J. Org. Chem. 2017, 82, 4793–4811.

Sponsors

Sponsors