title: C2 hydroxyl group governs the difference in hydrolysis rates of methyl-α-D-glycero-D-guloseptanoside and methyl-β-D-glycero-D-guloseptanoside.
abstract: 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.
authors.affiliation: Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Beck
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Miller
authors.forename: Mark W
authors.initials: MW
authors.lastname: Peczuh
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hadad
mesh_terms: D003198:Computer Simulation; D005960:Glucosides / Q000737:chemistry*; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008968:Molecular Conformation; D015394:Molecular Structure; D013816:Thermodynamics
chemical_list: D005960:Glucosides; C575054:methyl-alpha-D-glycero-D-guloseptanoside