jo202639g_si_001.pdf (1.33 MB)
Download file

C2 Hydroxyl Group Governs the Difference in Hydrolysis Rates of Methyl-α-d-glycero-d-guloseptanoside and Methyl-β-d-glycero-d-guloseptanoside

Download (1.33 MB)
journal contribution
posted on 04.05.2012, 00:00 by Jeremy M. Beck, Shawn M. Miller, Mark W. Peczuh, Christopher M. Hadad
A computational investigation into the hydrolysis of two methyl septanosides, methyl-α-d-glycero-d-guloseptanoside and methyl-β-d-glycero-d-guloseptanoside was undertaken. These septanosides were chosen as model compounds for comparison to methyl pyranosides and allowed direct comparison of α versus β hydrolysis rates for a specific septanoside isomer. Results suggest that hydrolysis takes place without proceeding through a transition state, an observation that was suggested in previous computational studies on exocyclic bond cleavage of carbohydrates. A conformational analysis of α- and β-anomers 1 and 2 and their corresponding oxocarbenium 3, coupled with relaxed potential energy surface (PES) scans (M06-2X/6-311+G**, implicit methanol), indicated that hydrolysis of the α-anomer is favored by 1–2 kcal/mol over the β-anomer, consistent with experiment. Model systems revealed that the lowest energy conformations of the septanoside ring system destabilize the β-anomer by 2–3 kcal/mol relative to the α-anomer, and the addition of a single hydroxyl group at the C2-position on a minimal oxepane acetal can reproduce the PES for the septanoside 1. These results suggest that the C2 hydroxyl plays a unique role in the hydrolysis mechanism, destabilizing the septanoside via its proximity to the anomeric carbon and also through its interaction with the departing methanol from the α-anomer via hydrogen-bonding interactions.