title: Determination of the Influence of Side-Chain Conformation on Glycosylation Selectivity using Conformationally Restricted Donors.
abstract: The synthesis of a series of conformationally locked mannopyranosyl thioglycosides in which the C6-O6 bond adopts either the gauche,gauche, gauche,trans, or trans,gauche conformation is described, and their influence on glycosylation stereoselectivity investigated. Two 4,6-O-benzylidene-protected mannosyl thioglycosides carrying axial or equatorial methyl groups at the 6-position were also synthesized and the selectivity of their glycosylation reactions studied to enable a distinction to be made between steric and stereoelectronic effects. The presence of an axial methoxy group at C6 in the bicyclic donor results in a decreased preference for formation of the β-mannoside, whereas an axial methyl group has little effect on selectivity. The result is rationalized in terms of through-space stabilization of a transient intermediate oxocarbenium ion by the axial methoxy group resulting in a higher degree of SN 1-like character in the glycosylation reaction. Comparisons are made with literature examples and exceptions are discussed in terms of pervading steric effects layered on top of the basic stereoelectronic effect.
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, MI, 48202, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Dharuman
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, MI, 48202, USA. dcrich@chem.wayne.edu.
authors.forename: David
authors.initials: D
authors.lastname: Crich
mesh_terms: D001597:Benzylidene Compounds / Q000737:chemistry*; D006031:Glycosylation; D008358:Mannose / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013865:Thioglycosides / Q000737:chemistry*
chemical_list: D001597:Benzylidene Compounds; D013865:Thioglycosides; D008358:Mannose
keywords: conformation; glycosylation; stereoelectronic effects; stereoselectivity; thioglycosides