Exploration of conformational flexibility and hydrogen bonding of xylosides in different solvents, as a model system for enzyme active site interactions

Abstract

The predominantly populated conformation of carbohydrates in solution does not necessarily represent the biologically active species; rather, any conformer accessible without too large an energy penalty may be present in a biological pathway. Thus, the conformational preferences of a naphthyl xyloside, which initiates in vivo synthesis of antiproliferative glycosaminoglycans, have been studied by using NMR spectroscopy in a variety of solvents. Equilibria comprising the conformations (4)C1, (2)SO and (1)C4 were found, with a strong dependence on the hydrogen bonding ability of the solvent. Studies of fluorinated analogues revealed a direct hydrogen bond from the hydroxyl group at C2 to the fluorine atom at C4 by a (1h)JF4,HO2 coupling. Hydrogen bond directionality was further established via comparisons of fluorinated levoglucosan molecules.

Conformational Plasticity in Glycomimetics: Fluorocarbamethyl‐L‐idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings

“…Recent efforts using O-substituted Ido compounds have providede nergy values in organic solvents. [27,28] However, given the intrinsic relative low energy barrierf or this equilibrium, NMR spectroscopic experiments in water using hydroxylated natural compounds have failed to slow down the equilibrium to provide quantitative and non-ambiguous values.…”

Exploring the Chemistry of Non‐sticky Sugars: Synthesis of Polyfluorinated Carbohydrate Analogues of d‐Allopyranose

“…The second route started with tosylate 21 , which was a suitable intermediate for the synthesis of compound 23 via intermediate 2,3‐anhydro 22 (49 % yield over two steps). The 2,4‐difluoroglucopyranose 13 was then formed in 8 % yield using potassium hydrogen fluoride . Given these disappointing results, we explored a third route starting with the formation of a bis‐tosylate intermediate followed by treatment under basic conditions leading to 1,6:3,4‐dianhydro‐2‐ O ‐ p ‐toluenesulfonyl‐β‐ d ‐galactose 24 in 93 % yield over two steps.…”

“…The 2,4-difluoroglucopyranose 13 was then formed in 8% yield using potassium hydrogen fluoride. [21] Given these disappointing results, we explored at hird route startingw ith the formation of ab is-tosylate intermediate [22] followed by treatment under basic conditions leadingt o1 ,6:3,4-dianhydro-2-O-p-toluenesulfonyl-b-d-galactose 24 in 93 %y ield over two steps. The latter compound represented the perfect candidate for ad ual nucleophilic fluorination.…”

Recent Advances in NMR Studies of Carbohydrates

“…Weak intramolecular OH…F H-bonds of monoand difluoro-substituted D-talo and D-iodopyranosides have been studied by Giuffredi and coworkers [104]. Conformation equilibrium of xyloside and n-deoxy-n-fluoro-substituted derivatives, bearing naphthyl aglycone, has been explored by R€ onnols et al [105]. Recently, Unione et al [106] investigated the conformational behavior of idose and glucose-like rings by low-temperature NMR experiments.…”