C-2 Oxyanion Participation in the Base-Catalyzed Cleavage of p-Nitrophenyl β-D-Galactopyranoside and p-Nitrophenyl α-D-Mannopyranoside¹

Abstract

p-Nitrophenyl 2-O-methyl-,3-~-galactopyranoside and p-nitrophenyl 2-O-methyl-a-~-mannopyranoside were synthesized and their cleavage reactions were compared with those of p-nitrophenyl @-D-galactopyranoside and p-nitrophenyl a-D-mannopyranoside. The cleavage rates (35-55 ") and products formed from these glycosides (all capable (of a tram-diaxial orientation a t C-1 and C-2) in methanolic and aqueous base solution were studied. Reaction of the glycosides in methanolic sodium methoxide resulted in over-all retention of configuration, whereas the 2-0-met:hylglycosides gave substantial amounts of p-nitroanisole and its reduction products (formed by secondary reaction with 2-0-methyl sugar). Kinetic studies included the effect of base concentration, the hydrogen isotope effect, ionic strength effects, and the effect of hydrogen peroxide. Blocking of the C-2 oxygen by a methyl group caused an enormous decrease in the rate of cleavage and a change in reaction pathway in both cases. The pnitrophenyl glycosides react by neighboring-group participation of the C-2 oxyanion, whereas the 2-0-methylglycoside reactions proceed, a t least in methanolic sodium methoxide, by bimolecular nucleophilic aromatic substitution.

Application of secondary .alpha.-deuterium kinetic isotope effects to studies of enzyme catalysis. Glycoside hydrolysis by lysozyme and .beta.-glucosidase

“…This value for the isotope effect is somewhat larger than that accepted for a purely S N~ reaction and probably reflects a small amount of carbonium ion character in the transition state. McClosky and Coleman (1945) and Gasman and Johnson (1966) have found that the yield of 1,6-anhydro-P-~-glucopyranose in the basic hydrolysis of aryl-P-glucosides decreases as the electron-withdrawing character of the aglycone is increased. This is consistent with the supposition that the basic solvolysis of G P involves partial carbonium ion character and that the extent of this is a function of the leaving group.…”

Mechanistic Investigations of Unsaturated Glucuronyl Hydrolase from Clostridium perfringens

“…Furthermore, the involvement of epoxide intermediates has been proposed to accelerate nonenzymatic decomposition of activated glycosides with a 1,2-trans arrangement under basic conditions (Fig. 6B) (41,42), and nonenzymatic opening of epoxides in a hexose is accelerated by participation of a nearby ester substituent (Fig. 6C) (43)(44)(45).…”

An Epoxide Intermediate in Glycosidase Catalysis

“…Interestingly, there is compelling evidence in support of neighboring group participation by a glycoside 2-hydroxyl and 1,2-anhydro sugars as intermediates in the alkaline cleavage of 1,2-trans glycosides and glycosyl fluorides. This data includes the wellknown differences in the rate of alkaline hydrolysis of 1,2-cis-versus 1,2-trans-glycosides, the reduced rate of alkaline hydrolysis of otherwise identical 2-alkylated 1,2-transglycosides 2 , and retention of anomeric stereochemistry in the alkaline methanolysis of 1,2trans-glycosyl fluorides whereas 2-alkylated 1,2-trans-glycosyl fluorides react with inversion 3 . Kinetic isotope effects for the alkaline hydrolysis of 4-nitrophenyl -Dmannopyranoside provided compelling evidence for neighboring-group participation by a C2-oxyanion 4 , and methods have recently been developed allowing for synthesis of 1,2anhydro sugars 5,6 .…”