The base-catalysed anomerization of dinitrophenyl glycosides: evidence for a novel reaction mechanism

Abstract

The mechanism of base-catalysed anomerization of per-0-acetylated 2, 4-dinitrophenyl-0-D-glucopyranoside in dimethy Isulfoxide has been investigated using a variety of techniques. A mechanism involving proton abstraction at C-1 was eliminated by the absence of proton exchange at that center and the measurement of a secondary deuterium kinetic isotope effect for the 1-deuterio substrate. A mechanism involving phenolate departure and recombination is rendered unlikely on the basis of remote substituent effects on the reaction rate and by the absence of any exchange of the phenyl moiety with added phenolate. A mechanism involving nucleophilic aromatic substitution initiated by an attack of the dimethylsulfinyl anion to generate a glucosyl oxyanion intermediate that anomerizes and recombines with the reactive aryl intermediate is consistent with the observations. This mechanism is further supported by the observation of a purple Meisenheimer complex intermediate and by the observed exchange between the substrate containing a labelled sugar moiety and added unlabelled 2,3,4,6-tetra-0-acetyl-P-D-glucopyranose.

Facile Synthesis of 2,4‐Dinitrophenyl α‐D‐Glycopyranosides as Chromogenic Substrates for α‐Glycosidases

“…This can then be converted to the α‐glycoside by treatment with a stronger base, such as potassium carbonate in solvents like DMF or DMSO 4. A mechanism for this isomerisation reaction, which involves nucleophilic aromatic substitution, was demonstrated by Berven et al5, 6…”

Imidazole Promoted Efficient Anomerization of β-D-Glucose Pentaacetate in Solid State and Reaction Mechanism

“…sugar ring-open reaction making dissociation of two anomers possible. 13 A key evidence is detection of N-acetylimidazole 3 in dilute deuterochloroform solution by NMR 13 ; and a further acetyl transfer to aliphatic alcohol was also observed, similar with enzyme catalyzed acyl transfer reaction under biological conditions 17 18 and he also suggested an acyl pyridinium specie like N-acetylimidazole 3 likely play a key role in pyridine-catalyzed anomerization 19 .…”

3,4-Dicyanophenyl 2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside

“…The precursor of the phthalocyanine-glucoconjugates is the title compound, 3,4-dicyanophenyl 2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside, which was prepared by the glycosidation method through nitrite displacement on substituted nitrophthalonitrile. The main products were exclusively the thermodynamically favored αanomers obtained by reversible SNAr reactions in polar aprotic solvents like Me 2 SO or DMF in the presence of a base (Berven et al, 1990). We report here the crystal structure of the title compound.…”

“…For related literature, see: Alvarez-Mico et al (2006; Burkhardt et al (2007); Ribeiro et al (2006); Huang et al (2005); Dinçer et al (2004); Berven et al (1990); Ocak et al (2004).…”