Complete kinetic isotope effect description of transition states for acid-catalyzed hydrolyses of methyl .alpha.- and .beta.-glucopyranosides

Abstract

The following kinetic isotope effects (klighf/khcavy) have been measured by the isotopic quasi-racemate method for the hydrolyses of methyl a-and 8-glucopyranosides, respectively in 2.0 M HCIOl at 80 "C (a-D 1.137 f 0.007, 1.089 f 0.006; 13-D 1.073 f 0.003, 1.045 f 0.004; y-D (C5) 0.987 f 0.002, 0.971 f 0.003; leaving group d, 1.006 f 0.001, 1.015 f 0.002; leaving group '*O 1.026 f 0.001, 1.024 f 0.001; ring I8O 0.9965 f 0.001, 0.991 f 0.002; anomeric I3C 1.007 f 0.001, 1.01 1 f 0.002).in conjunction with studies of the effect of added solutes on the rates of hydrolysis of various aldopyranosyl derivatives, which indicate such reactions are truely unimolecular, and model ring and @deuterium effects, it is possible to locate the dihedral angles about the 0 5 4 1 and CI-C2 bonds at the transition state using these data. If the dihedral angles so derived are used as constraints in calculations using N.L. Allinger's MM2 molecular mechanics program, transition-state structures are obtained. The geometry of these transition states stands in contradiction to the "theory of stereoelectronic control".Glycosyl transfer is a biologically important process.' This being so, the physical organic chemistry of acetal and of glycoside hydrolysis has received much Although the basic features of the mechanism of acid-catalyzed hydrolysis of glycopyranosides were established over 20 years ago,4 there remain unanswered questions with regard to the timing of bond-making and bond-breaking processes and with regard to stereochemistry, which are particularly pertinent to considerations of enzymic glycosyl t r a n~f e r .~ Since isotopic substitution does not in general alter the potential energy surface for a reaction,6 kinetic isotope effects are the ideal method for addressing these questions. We accordingly elected to measure the kinetic isotope effects on the acid-catalyzed hydrolyses of methyl CY-and P-glucopyranosides, corresponding to the isotopic substitution pattern as shown in structure I. IThe acid-catalyzed hydrolysis of glucopyranosides is known4 to proceed by specific acid catalysis, the exocyclic oxygen atom being reversibly protonated and then the Cl-oxygen bond cleaving. Since the leaving group oxygen atom is completely protonated before glycone-aglycone fission begins, the magnitude of the leaving group lSO kinetic isotope effect is a direct measure of the extent to which the glycone-aglycone bond is broken at the transition state.' Any ring lSO effect will arise because the endocyclic C1-0 bond acquires double-bond character at the transition state as the positive charge on C1 is delocalized by one of the oxygen lone pairs of electrons. It will thus be inverse ( k l 6 / k I s < I.()), and its magnitude will reflect the degree of double-bond character of the C1-0 bond and hence the charge on oxygen. The magnitude of the I3C kinetic isotope effect will, in the absence of nulceophilic participation, reflect the degree to which breaking of the glycone-aglycone bond is compensated for by the tightening C1-05 bond.6There are...

A Historical Perspective for the Catalytic Reaction Mechanism of Glycosidase; So As to Bring about Breakthrough in Confusing Situation

“…The SDKIEs for the non-enzymatic reactions in acidcatalyzed hydrolysis also have been examined using methyl -and -glucosides substituted deuterium at C 1 -, C 2 -, and C 5 -hydrogen atoms of glycones, the kinetic isotope effects of which are designated -, -, andSDKIEs, 27,40) respectively. In the non-enzymatic reaction for methyl -and -glucosides (solvolysis, 2.0 M HClO 4 at 80 C), the -and -SDKIEs for both substrates are observed to be k H /k D values of 1.13 and 1.11, while those for methyl -glucoside are 1.09 and 1.05, respectively, but no -SDKIEs were noticed in either substrate.…”

Transition States for Glucopyranose Interconversion

“…The [1-13 C]glucose and [5][6][7][8][9][10][11][12][13][14][15][16][17][18] O]glucose equilibrium isotope effects were determined by 13 C-NMR as in Lewis and Schramm 20 . Magnetic lock was obtained by including deuterium oxidefilled coaxial insert with the cuvette and experimental solution.…”

“…Schmid 36 treated the reaction as a single step and found values similar to the present data for heat and entropy of activation in glucose anomerization (17.2 kcal/mol and -24 cal/mol K, respectively). It has also been noted that the slow isotope exchange of [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] O]D-glucose in water as compared to mutarotation rates definitively rules out a significant role of an aldehydrol form 37,38 , although this form has been observed in solution 39 with the other tautomers.…”

“…The solvent KIE expected from their one-water model was 8.6 and from their two-water model was approximately 20. The primary [1-13 C] and [5][6][7][8][9][10][11][12][13][14][15][16][17][18] O] KIE expected from their one-water transition states were 1.011 and 1.013, reflecting considerably more ring-opening than seen experimentally.…”

The 4-aza-S-ribosyl-L-homocysteine Derivatives and the Related Gamma-lactam and Azahemiacetal Analogs: Synthesis, Inhibition and Quorum Sensing Activity

“…152 Moreover such observation was attested by potent inhibition observed by lactam and lactone analogs although they only mimic the hybridization but not the charge.…”