The p-methoxybenzyl ether as an in situ-removable carbohydrate-protecting group: a simple one-pot synthesis of the globotetraose tetrasaccharide

Abstract

A one-pot synthesis of the globotetraose tetrasaccharide is reported. The synthetic method relies on the use of a p-methoxybenzyl ether as an in situ-removable protecting group. N-Iodosuccinimide/trifluoromethanesulfonic acid-promoted glycosylation of 2-bromoethyl-2,3,6-tri-O-benzoyl-4-O-(2,3,6-tri-O-benzoyl-β-D-galactopyranosyl)-β-D-glucopyranoside 5 at −45 °C with phenyl 2,4,6-tri-O-benzyl-3-O-(4-methoxybenzyl)-1-thio-β-D-galactopyranoside 6 gives an intermediate trisaccharide from which the p-methoxybenzyl ether is removed by allowing the reaction temperature to rise to 0 °C for 40 min. Again lowering the temperature to −45 °C, followed by addition of methyl 3,4,6-tri-O-acetyl-2-trichloroethoxycarbonylamino-2-deoxy-1-thio-β-D-galactopyranoside 8, affords the globotetraose tetrasaccharide 11 in one-pot in an excellent yield of 76%.