title: The stereodirecting effect of the glycosyl C5-carboxylate ester: stereoselective synthesis of beta-mannuronic acid alginates.
abstract: Glycosylations of mannuronate ester donors proceed highly selectively to produce the 1,2-cis-linked products. We here forward a mechanistic rationale for this counterintuitive selectivity, based on the remote stereodirecting effect of the C5-carboxylate ester, which has been demonstrated using pyranosyl uronate ester devoid of ring substituents other than the C5- carboxylate ester. It is postulated that the C5-carboxylate ester prefers to occupy an axial position in the oxacarbenium intermediate, thereby favoring the formation of the (3)H4 half-chair over the (4)H3 conformer. Nucleophilic attack on the (3)H4 half-chair intermediate occurs in a beta-fashion, providing the 1,2-cis-mannuronates with excellent stereoselectivity. The potential of the mannuronate ester donors in the formation of the beta-mannosidic linkage has been capitalized upon in the construction of a mannuronic acid alginate pentamer using a convergent orthogonal glycosylation strategy.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands. jcodee@chem.leidenuniv.nl
authors.forename: Jeroen D C
authors.initials: JD
authors.lastname: Codée
authors.forename: Leendert J
authors.initials: LJ
authors.lastname: van den Bos
authors.forename: Ana-Rae
authors.initials: AR
authors.lastname: de Jong
authors.forename: Jasper
authors.initials: J
authors.lastname: Dinkelaar
authors.forename: Gerrit
authors.initials: G
authors.lastname: Lodder
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
mesh_terms: D000464:Alginates / Q000138:chemical synthesis* / Q000737:chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D006031:Glycosylation; D006603:Hexuronic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D013237:Stereoisomerism
chemical_list: D000464:Alginates; D002264:Carboxylic Acids; D004952:Esters; D006603:Hexuronic Acids; C008324:mannuronic acid