Solid-phase synthesis of a branched hexasaccharide using a highly efficient synthetic strategy.
The solid-phase synthesis of branched lacto-N-neohexaose derivative 1 occurring in human milk is described. The new building block of lactose 3 bearing the orthogonal temporary hydroxy protecting groups 9-fluorenylmethyloxycarbonyl (Fmoc) and levulinoyl (Lev) has been prepared. Its use, together with that of lactosamine donor 4, glucosamine donor 5, and O-galactosyl trichloroacetimidate 6, has enabled the preparation of hexasaccharide 22 following two different approaches in excellent overall yield (43%, 90% per step over eight steps). An additional key feature of this work is the successful use of newly prepared ester-type linker 2, having a benzylic spacer connected to the anomeric oxygen. This linker presents the advantage of producing a benzylic anomeric moiety after cleavage from the polymer support, which could be easily removed to obtain the unprotected oligosaccharide 1.
Roussel
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F
Fachbereich Chemie, Universität Konstanz, Fach M 725, D-78457 Konstanz, Germany.
Takhi
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M
Schmidt
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RR
D002240:Carbohydrate Sequence; D003432:Cross-Linking Reagents; D004952:Esters / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry; D005944:Glucosamine / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D008895:Milk, Human / Q000737:chemistry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis*
D003432:Cross-Linking Reagents; D004952:Esters; D005449:Fluorenes; D009844:Oligosaccharides; C054007:1-(9-fluorenyl)methyl chloroformate; D007785:Lactose; D005944:Glucosamine