Hydrolysis of (2-Deoxy-α-d-Glucopyranosyl)pyridinium Salts:  The 2-Deoxyglucosyl Oxocarbenium Is Not Solvent-Equilibrated in Water

Abstract

The hydrolysis reactions of four 2-deoxy-R-D-glucopyranosyl pyridinium salts exhibit first-order rate constants that are independent of pH in the range of 4.4-10.5 pH units. Derived second-order rate constants for the hydrolysis reactions of 2-deoxy-R-D-glucopyranosyl 4′-bromoisoquinolinium tetrafluoroborate (4d) conducted in the presence of nucleophilic monoanions (µ ) 2.0) including AcO -, Cl -, Br -, and N 3exhibit a Swain-Scott parameter (s) of 0.03 ( 0.10, indicating that these reactions show no sensitivity to the nature of the anion. In the presence of azide ion, a substantial quantity of the 2-deoxy-R-glucopyranosyl 4′-bromoisoquinolinium salt hydrolysis product results from a post rate-limiting reaction of a cationic intermediate with azide. Analysis of the hydrolysis product ratios indicates that the 2-deoxyglucosyl oxocarbenium ion is not solvent-equilibrated in water. Furthermore, the reaction of solvent occurs about 2-fold faster with the cationic intermediate that is formed during solvolysis of the β-anomeric salt than with the corresponding intermediate produced from the reactions of the R-anomer 4d.

Aspects of Glycosidic Bond Formation in Aqueous Solution: Chemical Bonding and the Role of Water

“…This is similar to the proposed transition states for corresponding hydrolysis of methyl b-d-glucopyranoside. [1,2,8] At the transition state the C 1 -O 1 distance was % 1.9 indicating the degree of bond C 1 the transition state must be regarded as an early one, which is consistent with a late transition state for the back reaction. [2,5,6] The stability range of the oxocarbenium cation can also be roughly inferred from the shape of the free energy profile, see Figure 8, from values of x close to the maximum (where the transition state exists).…”

“…Subsequently, the number of water molecules was decreased (by using NVT and NpT simulations at 300 K and 1 atm) from 483 to 89, 73, 57, and 44 solvating molecules. No significant difference was found between the radial distribution function of water oxygen atoms around both C 1 and O 1 as obtained by 89, 73, 57 molecules, whereas qualitative deviations were found with 44 molecules. In order to prepare a starting configuration for the follow-up ab initio simulations a configuration was sampled from a NpT run (within a cubic supercell) with 57 water molecules where O m was close to the C 1 -O 1 vector subject to having system parameters such as volume and total potential energy close to their respective average values.…”

“…Simple sugars make up a wide variety of substances found in nature, from DNA to cellulose to biological energy storage mechanisms. Consequently, the glycosidic bond has been studied experimentally for a wide variety of compounds, [1][2][3][4][5][6][7][8][9][10][11][12][13] predominantly through hydrolysis, under a myriad of conditions, and is important in the consideration of enzymatic glycosyl-transfer reactions. One of the reasons it has been studied so extensively is because of the rich and often subtle variety of the reactions that take place.…”

“…Adding to the complexity are competing hydrolysis reactions when multiple products are possible. [1] It is accepted that the reaction proceeds through an oxocarbenium cation intermediate; the mechanism involved in hydrolysis of glucopyranosides has been concluded to be dissociative (D N +A N ) or partially-dissociative (A * N D N ) [1,2,13] which lies between S N 2 and S N 1 behavior, although a concerted mechanism (A N D N ) [5,6] has been observed for the case of aqueous hydrolysis of fluoro-a-d-glucopyranoside (see ref. [14,15] for notation details).…”

Structural and Computational Analysis of 2‐Halogeno‐Glycosyl Cations in the Presence of a Superacid: An Expansive Platform

“…[6] The fluorine substituent has also been strategically employed to direct glycosylation selectivity,p articularly when matched with protecting-group electronics. [10,11] Thes ynergistic electronwithdrawing effect of ah alogen atom at C2 likely enhances this global effect by rendering the anomeric carbon atom even more electron deficient. [8] Unlike simple oxocarbenium ions that are of comparable stability to benzylic ions, [9] thee nvironment of the pyranose ring, containing multiple CÀOb onds,r educes the stability and lifetime of these ionic species.…”