Solid-phase synthesis of a branched hexasaccharide using a highly efficient synthetic strategy

The solid-phase synthesis of branched lacto-N-neohexaose derivative 1 occur ring in human milk is described. The new building block of lactose 3 bearin g the orthogonal temporary hydroxy protecting groups 9-fluorenylmethyloxyca rbonyl (Fmoc) and levulinoyl (Lev) has been prepared. Its use, together wit h that of lactosamine donor 4, glucosamine donor 5, and O-galactosyl trichl oroacetimidate 6, has enabled the preparation of hexasaccharide 22 followin g two different approaches in excellent overall yield (43%, 90% per step ov er eight steps). An additional key feature of this work is the successful u se of newly prepared ester-type linker 2, having a benzylic spacer connecte d to the anomeric oxygen. This linker presents the advantage of producing a benzylic anomeric moiety after cleavage from the polymer support, which co uld be easily removed to obtain the unprotected oligosaccharide 1.