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

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-alpha/beta -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 G1cNAc(beta1 -->6)GlcOAc was isolated. Similarly the 4,6-O-phenylboronate diester of ethyl 1-thio-beta -D-galactopyranoside was regio selectively 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-beta -D-galactopyranoside. Through a similar sequence of glycosylation of (MPEG)(DOX)OH, MCPM deprotection, glycosylation, functional group manipulation and cleavage the peracylated disaccharide GlcNAc(beta1 -->3)Gal(beta1 --> )DOXOAc was prepared. Finally, the donor 2,6-di-O-benzoyl-4-O-levulinoyl-3-O-(R,S-1-methyl 1 ' -cyclopropylmethyl)-1-thio-beta -D-galactopyranoside was prepared and elaborated into the trisaccharide GlcNAc(beta1 -->3)[Glc(beta -->4)]Ga1(beta1 --> )DOXOH. This trisaccharide was elaborated into the pentasaccharide Neu5Ac(alpha2 -->3)Gal(beta1 -->4)GlcNAc(beta1 -->3) [Glc(beta1 -->4)]Gal(beta1 --> )DOXOH using GalE-LgtB fusion and CNP-Neu5Ac synthetase/sialyltransferase fusion enzymes. This pentasaccharide is a single repeat unit of the capsular polysaccharide of Group B Streptococcus type 1A. (C) 2001 Elsevier Science Ltd. All rights reserved.