Polymer-Supported Synthesis of a Branched Trisaccharide of the Type IA Group B Streptococcus Capsular Polysaccharide: 3-Iodo-4-methoxybenzyl as a New O-Protecting Group

The synthesis of a key branched trisaccharide (1), of the type IA Group B Streptococcus capsular polysaccharide is described. The monomethyl ether of polyethylene glycol (MeO–(CH2CH2O)n–H, MPEG) and dioxyxylene [p-(O)CH2–C6H4–CH2(O)–, DOX] have been used as the polymer-support/linker combination. Attempts to use the p-methoxybenzyl (PMB) protecting group under glycosylation conditions involving N-iodosuccinimide/silver trifuoromethanesulfonate promotion resulted in iodination to form the 3-iodo-4-methoxybenzyl (IPMB) derivative. Subsequently IPMB chloride was independently synthesized and used to introduce this new protecting group. The levulinoyl and the IPMB protecting groups have been used in an orthogonal manner to create 3,4-branching on a galactopyranosyl residue. Due to the enhanced acid stability of the IPMB group over the PMB group, the former group was critical to the success of the synthesis. The final trisaccharide and its intermediates were cleaved from the MPEG polymer-support by scandium(III)trifluoromethanesulfonate and acetic anhydride.