Dissecting the Influence of Oxazolidinones and Cyclic Carbonates in Sialic Acid Chemistry

Abstract

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.

Synthesis and intramolecular glycosylation of sialyl mono-esters of o-xylylene glycol. The importance of donor configuration and nitrogen protecting groups on cyclization yield and selectivity; isolation and characterization of a N-sialyl acetamide indicative of participation by acetonitrile

“…These observations are consistent with intermolecular glycosylations conducted with the corresponding methyl esters in which the N -acetyloxazolidinone 8,17 and isothiocyanate systems 11 are among the most equatorially selective of sialyl donors described to date. Accordingly, we attribute the higher equatorial selectivity observed with 9 and 12 to the stabilization of S N 2-like transition states for cyclization akin to 17 with respect to the corresponding oxocarbenium ion by the more electron-withdrawing N -acetyl oxazolidinone 37 and isothiocyanate groups. 11 …”

A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art

“…28 In this method the energy required to fragment a series of glycosyl donors to the corresponding oxocarbenium ions in a mass spectrometer is related to the relative destabilization of the oxocarbenium ions by the different protecting group systems deployed. In this manner, by determining the minimum cone energies required for fragmentation in a TOF-ESI mass spectrometer (Fig.…”

“…The consequent retardation of S N 1-type mechanisms by the presence of such protecting groups favors associative processes leading to the high selectivities they typically exhibit. 28 …”

“…Selectivity, therefore, is likely achieved via an associative S N 2-like mechanism via displacement of either acetonitrile from a covalent nitrilium ion or a triflate anion from a glycosyl triflate. 28 The use of the oxazolidinone-protected sialyl donors has recently enabled highly α-selective sialidation reactions to be conducted on polymer-supported acceptors. 54 …”

The Isothiocyanato Moiety: An Ideal Protecting Group for the Stereoselective Synthesis of Sialic Acid Glycosides and Subsequent Diversification

“…First, as the isothiocyanate group is considerably more polar than the azido and isocyanate groups (dipole moments of C 6 H 5 N 3 , C 6 H 5 N=C=O, and PhN=C=S in Debye units, respectively: 1.82, 2.43, 2.69 [14] ), it is possible that the isothiocyanate simply serves as a strongly electron-withdrawing group and promotes S N 2 glycosylation as has been proposed [15] for the oxazolidinone system. Alternatively, consistent with current models for the through-space stabilization of glycosyl oxocarbenium ions, [16] it is possible that a transient intermediate sialyl oxocarbenium ion preferentially adopts the 5 H 4 conformation 15 benefitting from stabilization by the pseudoaxial 4- O -acetate and the isothiocyanate groups, with the latter providing significant steric shielding to the β-face (Figure 1).…”