A general strategy for stereoselective glycosylations.
The principal challenge that the synthesis of oligosaccharides of biological importance presents is the development of a general approach for the stereoselective introduction of a glycosidic linkage. It is shown here that a (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety at C-2 of a glycosyl donor can perform neighboring group participation to give a quasi-stable anomeric sulfonium ion. Due to steric and electronic factors, the sulfonium ion is formed as a trans-decalin ring system. Displacement of the sulfonium ion by a hydroxyl leads to the stereoselective formation of alpha-glycosides. NMR experiments were employed to show convincingly the presence of the beta-linked sulfonium ion intermediate. The (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety could be introduced by reaction of a sugar alcohol with acetic acid (1S)-phenyl-2-(phenylsulfanyl)ethyl ester in the presence of BF(3)-OEt(2). Furthermore, it could be removed by conversion into acetate by treatment with BF(3)-OEt(2) in acetic anhydride. The introduction as well as the cleavage reaction proceeds through the formation of an intermediate episulfonium ion. The use of the new methodology in combination with traditional neighboring group participation by esters to introduce beta-glycosides makes it possible, for the first time, to synthesize a wide variety of oligosaccharides by routine procedures. The latter was demonstrated by the synthesis of the Galili trisaccharide, which has been identified as an epitope that can trigger acute rejections in xeno-transplantations, by the one-pot two-step glycosylation sequence.
Kim
Jin-Hwan
JH
Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, USA.
Yang
Hai
H
Park
Jin
J
Boons
Geert-Jan
GJ
D002236:Carbohydrate Conformation; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013452:Sulfonium Compounds / Q000737:chemistry; D014312:Trisaccharides / Q000138:chemical synthesis*
D000939:Epitopes; D006027:Glycosides; D013452:Sulfonium Compounds; D014312:Trisaccharides