Conformational Domino Effect in Saccharides: A Prediction from Alkyl β-(1→6)-Diglucopyranosides

Abstract

A series of alkyl beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosides, containing nonchiral and chiral aglycons, were synthesized and analyzed by NMR and CD. The results, collected from four sets of disaccharides, demonstrated that the rotational properties of the interglycosidic linkage depend on the structural natures of both the aglycon and the solvent. Stereoelectronic and steric factors explain this rotational dependence, the gauche- trans (gt) rotamer being the most stable. Furthermore, correlations between Taft's steric parameters or between the pKa values of the alkyl substituent (aglycon) versus corresponding rotamer populations were observed. These results point to a natural conformational domino effect in oligosaccharides, where the conformational properties of each (1-->6) interglycosidic linkage will depend on the structure of the previous residue or its aglycon. In addition, a very weak rotational population dependence of the hydroxymethyl group at residue II on the aglycon at residue I was observed. The population of the gauche- gauche (gg) rotamer decreased, and that of gt increased as the Taft's steric parameters of the remote aglycon increased, independently of the disaccharide series and of the solvent.

Conformational properties of glucose-based disaccharides investigated using molecular dynamics simulations with local elevation umbrella sampling

“…Finally, for the (1?6)-linked disaccharides (I and G), the w values are generally found in the range [160°; 180°]. The existence of two alternative conformations at equilibrium (differing in the value of thex dihedral angle) for the (1?6)-linked disaccharides (I and G) also agrees with the results from NMR measurements 91,96,192,193 and independent simulations. 58 91,96 Note that independent results for G analogs in nonaqueous polar solvents also support an approximate [0:40:60] ratio.…”

“…These are the conformations usually referred to as gt and gg, respectively (the first letter corresponding tox and the second to x; Section 2.3). The (near) absence of the tg conformer, also evidenced by NMR, 91,96,[182][183][184][185][186][187][188][189][190][191][192][193]194 and X-ray crystallography 195,196 experiments, is a wellknown feature of D-hexopyranoses and D-hexopyranosides presenting the gluco configuration (or C 2 or/and C 3 epimer thereof). As discussed in details elsewhere, 48 however, the exact origin of this conformational preference is still a matter of discussion, different authors invoking distinct effects as a main cause (e.g., the gauche effect, [197][198][199]185,200,201 intramolecular H-bonding, 185,188,202 1,3-syn-diaxial repulsion with the C 4 hydroxyl group, 197,199,185 or specific solvation effects 188,[203][204][205][206][207][208][209]201 ).…”

“…58 91,96 Note that independent results for G analogs in nonaqueous polar solvents also support an approximate [0:40:60] ratio. 192,193 The Ramachandran free-energy maps (Figs. 3 and 4) are also found to present a good qualitative agreement with corresponding MM3 adiabatic maps [117][118][119][120][121]123 and GLYCAM04 maps in vacuum 150 for the different disaccharides.…”

Synthesis of Novel Pyran Fragments to Incorporate into Peloruside Analogues

“…The use of suitably protected glycals in Ferrier transformations is well precedented in literature and has been reported by numerous different groups. [55][56][57][58][59] In general, the Ferrier reaction requires the glycal to have an acetate group, or a similar carbonyl based protecting group, at the C3 position to be activated by a Lewis acid and act as a leaving group (Scheme 10). Based on this, it was decided that the hydroxyl group at C3 must be protected using an acetyl group to facilitate the Ferrier transformation.…”

“…Based on a procedure from Roën et al, the D-glucal was to be protected at positions C4 and C6 using anisaldehyde dimethyl acetal and catalytic amounts of pyridinium p-toluenesulfonate. 56 This was to be followed by the same acetylation procedure, that had been used in the trityl protection route, from Adinolfi et al 55 Ferrier transformations were to be done using the weaker Lewis acids, iodine and indium tribromide as the PMP acetal protecting group is known to be relatively acid labile. 72 If the acetal was to remain stable under the Lewis acid conditions, the bicyclic dioxolane-pyran ring system would not be expected to form as the C6 oxygen is unable to reach the position required to attack the C1 (Scheme 16).…”