title: Mechanistic studies on the stereoselective formation of beta-mannosides from mannosyl iodides using alpha-deuterium kinetic isotope effects.
abstract: Stereoselective synthesis of beta-mannosides is one of the most challenging linkages to achieve in carbohydrate chemistry. Both the anomeric effect and the C2 axial substituent favor the formation of the axial glycoside (alpha-product). Herein, we describe mechanistic studies on the beta-selective glycosidation of trimethylene oxide (TMO) using mannosyl iodides. Density functional calculations (at the B3LYP/6-31+G(d,p):LANL2DZ level) suggest that formation of both alpha- and beta-mannosides involve loose S(N)2-like transition-state structures with significant oxacarbenium character, although the transition structure for formation of the alpha-mannoside is significantly looser. alpha-Deuterium kinetic isotope effects (alpha-DKIEs) based upon these computed transition state geometries match reasonably well with the experimentally measured values: 1.16 +/- 0.02 for the beta-linkage (computed to be 1.15) and 1.19 +/- 0.05, see table 2 for the alpha-analogue (computed to be 1.26). Since it was unclear if beta-selectivity resulted from a conformational constraint induced by the anomeric iodide, a 4,6-O-benzylidine acetal was used to lock the iodide into a chairlike conformation. Both experiments and calculations on this analogue suggest that it does not mirror the behavior of mannosyl iodides lacking bridging acetal protecting groups.
authors.affiliation: University of California, Davis, Department of Chemistry, One Shields Avenue, Davis, California 95616, USA.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: El-Badri
authors.forename: Dan
authors.initials: D
authors.lastname: Willenbring
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Tantillo
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Gervay-Hague
mesh_terms: D000107:Acetylation; D002244:Carbon / Q000737:chemistry; D003903:Deuterium / Q000737:chemistry*; D006031:Glycosylation; D007454:Iodides / Q000737:chemistry*; D007700:Kinetics; D008362:Mannosides / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D007454:Iodides; D008362:Mannosides; D002244:Carbon; D003903:Deuterium; D010100:Oxygen