Efficient selective preparation of methyl-1,2,4-tri-O-acetyl-3-O-benzyl-β-l-idopyranuronate from methyl 3-O-benzyl-l-iduronate

Methyl 1,2,4-tri-O-acetyl-3-O-benzyl-l-idopyranuronate 6β/6α, prepared from methyl 3-O-benzyl-l-iduronate (4), is a key synthon in heparin/heparan sulfate synthesis. The 1H and 13C NMR spectra of the furanose–pyranose mixture of 4, after dissolution and equilibration in d4-methanol, were fully assigned allowing to expect that 4 could crystallise in the β-pyranose form. New acetylation conditions able to trap this form were subsequently devised, allowing the isolation of 83% of pure 6β by simple crystallisation, along with 9% of the 6β/6α mixture. This represents a major advantage over the previously published procedure, especially on multigram scales.