title: Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions.
abstract: Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Yongho
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Kaid C
authors.initials: KC
authors.lastname: Harper
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kuhl
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Kwan
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. jacobsen@chemistry.harvard.edu.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Jacobsen
mesh_terms: D002384:Catalysis; D006027:Glycosides / Q000138:chemical synthesis*; D006031:Glycosylation; D013237:Stereoisomerism; D013890:Thiourea / Q000031:analogs & derivatives*
chemical_list: D006027:Glycosides; D013890:Thiourea