Two N-acetyl
4O,5N-oxazolidine-protected sialyl
thioglycosides epimeric at the 7-position have been synthesized and their
reactivity and stereoselectivity in glycosylation reactions compared. It is
demonstrated that the natural 7S-donor is both more reactive
and more α-selective than the unnatural 7R-isomer. The
difference in reactivity is attributed to the side chain conformation and
specifically to the proximity of O7 to the anomeric center. In the natural
7S-isomer O7 is closer to the anomeric center than in its
unnatural 7R-epimer and therefore better able to support
incipient positive charge at the locus of reaction. The difference in
selectivity is also attributed to the side conformation, which in the unnatural
7R-series is placed perpendicularly above the α-face
of the donor and so shields it to a greater extent than in the
7S-series. These observations are consistent with earlier
conclusions on the influence of the side chain conformation on reactivity and
selectivity derived from conformationally locked models in the glucose and
galactose series and corroborate the suggestion that those effects are
predominantly stereoelectronic rather than torsional. The possible relevance of
side chain conformation as a factor in the influence of glycosylation
stereoselectivity by remote protecting groups and as a control element in
enzymic processes for glycosidic bond formation and hydrolysis are discussed.
Methods for assignment of the anomeric configuration in the sialic acid
glycosides are critically surveyed.
At a moment′s notice: Thermal equilibration of 1 and mass spectral analysis of sialyl phosphates suggest that the 4O,5N‐oxazolidinone and the 4,5‐O‐carbonate systems influence the anomeric effect and the mechanisms of sialidation by virtue of their dipole moment in the mean plane of the pyranose ring. The electron‐withdrawing effect destabilizes 2 and promotes associative glycosylation mechanisms. TEMPO=2,2,6,6‐tetramethylpiperidine N‐oxide.
A reagent system comprising tetrabutylammonium nitrate-trifluoroacetic anhydride-triethylamine has been developed for the synthesis of 2-nitroglycals from various protected glycals. The base-catalyzed Ferrier rearrangement on tri-O-acetylated 2-nitroglycals has been reported for the first time. Reactivity of these nitroacetates and associated selectivity has been examined, and some of the products have been converted into 2,3-diamino-2,3-dideoxyglycosides and methyl N-acetyl-D-lividosaminide.
A method
for the investigation of the influence of protecting groups
on the anomeric equilibrium in the sialic acid glycosides has been
developed on the basis of the equilibration of O-sialyl
hydroxylamines by reversible homolytic scission of the glycosidic
bond following the dictates of the Fischer–Ingold persistent
radical effect. It is found that a trans-fused 4O,5N-oxazolidinone group stabilizes the
equatorial glycoside, i.e., reduces the anomeric effect, when compared
to the 4O,5N-diacetyl protected
systems. This effect is discussed in terms of the powerful electron-withdrawing
nature of the oxazolidinone system, which in turn is a function of
its strong dipole moment in the mean plane of the pyranose ring system.
The new equilibration method displays a small solvent effect and is
most pronounced in less polar media consistent with the anomeric effect
in general. The unusual (for anomeric radicals) poor kinetic selectivity
of anomeric sialyl radicals is discussed in terms of the planar π-type
structure of these radicals and of competing 1,3-diaxial interactions
in the diastereomeric transition states for trapping on the α-
and β-faces of the radical.
A new organocatalytic glycosylation method exploiting the lactol functionality has been disclosed. The catalytic generation of glycosyl oxacarbenium ions from lactols under forcible conditions via weakly Brønsted-acidic, readily available secondary amine salts affects the diastereoselective glycosylation of 2-deoxypyranoses and furanoses. This operationally simple iminium catalyzed activation of 2-deoxy hemi-acetals is a potential alternative to the existing cumbersome methods that need specialized handling. The mechanisms for this unique transformation and kinetic/thermodynamic effects have been discussed based on both experimental evidence and theoretical studies.
We demonstrate here
that the strained and bulky protonated 2,4,6-tri-tert-butylpyridine salts serve as efficient catalysts for
highly stereoselective glycosylations of various glycals. Moreover,
the mechanism of action involves an interesting single hydrogen bond
mediated protonation of glycals and not via the generally conceived
Brønsted acid pathway. The counteranions also play a role in
the outcome of the reaction.
A new reagent system comprising acetyl chloride, silver nitrate, and acetonitrile has been developed for the synthesis of 2-nitroglycals from the corresponding glycals. Under certain conditions, the formation of 2-nitro-1-acetamido sugars has also been observed. In addition, a few other non-carbohydrate-derived olefins also gave the corrresponding conjugated nitroolefins.
The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Herein, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides rather than monosaccharides as minimal precursors greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the “sulfation code” and understanding the roles of specific GAG structures in physiology and disease.
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