1-Methyl 1′-cyclopropylmethyl: An acid labile O-protecting group for polymer-supported oligosaccharide synthesis

Article abstract of DOI:10.1016/S0040-4020(01)00582-8

R,S-1-Methyl 1′-cyclopropylmethanol can be converted to its trichloroacetimidate derivative. Lewis acid catalyzed etherification can then be used to prepare methyl cyclopropylmethyl (MCPM) ethers. Thus, ethyl 2,3,4-tri-O-benzyl-6-O-(R,S-1-methyl 1′-cyclopropylmethyl)-1-thio-α/β-D-glucopyranoside was prepared and the linker polymer combination (MPEG)(DOX)OH glycosylated. The MCPM group was cleaved with 10% trifluoroacetic acid in CH₂Cl₂ and the resulting alcohol glycosylated. After protecting group manipulations and cleavage the peracetylated disaccharide GlcNAc(β1→6)GlcOAc was isolated. Similarly the 4,6-O-phenylboronate diester of ethyl 1-thio-β-D-galactopyranoside was regioselectively etherified at O-3 and after boronate cleavage the sugar benzoylated to give ethyl 2,4,6-tri-O-benzoyl-3-O-(R,S-1-methyl 1′-cyclopropylmethyl)-1-thio-β-D-galactopyranoside. Through a similar sequence of glycosylation of (MPEG)(DOX)OH, MCPM deprotection, glycosylation, functional group manipulation and cleavage the peracylated disaccharide GlcNAc(β1→3)Gal(β1→)DOXOAc was prepared. Finally, the donor 2,6-di-O-benzoyl-4-O-levulinoyl-3-O-(R,S-1-methyl 1′-cyclopropylmethyl)-1-thio-β-D-galactopyranoside was prepared and elaborated into the trisaccharide GlcNAc(β1→3)[Glc(β1→4)]Gal(β1→)DOXOH. This trisaccharide was elaborated into the pentasaccharide Neu5Ac(α2→3)Gal(β1→4)GlcNAc(β1→3) [Glc(β1→4)]Gal(β1→)DOXOH using GalE-LgtB fusion and CMP-Neu5Ac synthetase/sialyltransferase fusion enzymes. This pentasaccharide is a single repeat unit of the capsular polysaccharide of Group B Streptococcus type 1A.