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Conformational Plasticity in Glycomimetics: Fluorocarbamethyl‐ L ‐idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings
Author(s) -
Unione Luca,
Xu Bixue,
Díaz Dolores,
MartínSantamaría Sonsoles,
Poveda Ana,
Sardinha João,
Rauter Amelia Pilar,
Blériot Yves,
Zhang Yongmin,
Cañada F. Javier,
Sollogoub Matthieu,
JiménezBarbero Jesus
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201501249
Subject(s) - chemistry , conformational isomerism , nuclear magnetic resonance spectroscopy , dynamic equilibrium , molecular dynamics , computational chemistry , stereochemistry , molecule , organic chemistry
Sugar function, structure and dynamics are intricately correlated. Ring flexibility is intrinsically related to biological activity; actually plasticity in L ‐iduronic rings modulates their interactions with biological receptors. However, the access to the experimental values of the energy barriers and free‐energy difference for conformer interconversion in water solution has been elusive. Here, a new generation of fluorine‐containing glycomimetics is presented. We have applied a combination of organic synthesis, NMR spectroscopy and computational methods to investigate the conformational behaviour of idose‐ and glucose‐like rings. We have used low‐temperature NMR spectroscopic experiments to slow down the conformational exchange of the idose‐like rings. Under these conditions, the exchange rate becomes slow in the 19 F NMR spectroscopic chemical shift timescale and allows shedding light on the thermodynamic and kinetic features of the equilibrium. Despite the minimal structural differences between these compounds, a remarkable difference in their dynamic behaviour indeed occurs. The importance of introducing fluorine atoms in these sugars mimics is also highlighted. Only the use of 19 F NMR spectroscopic experiments has permitted the unveiling of key features of the conformational equilibrium that would have otherwise remained unobserved.