Short Synthesis of Idraparinux by Applying a 2‐O‐Methyl‐4,6‐O‐arylmethylene Thioidoside as a 1,2‐trans‐α‐Selective Glycosyl Donor

Abstract

The fully O‐sulfated, O‐methylated, heparin‐related anticoagulant pentasaccharide idraparinux was prepared by a new synthetic pathway in 38 steps using d‐glucose and methyl α‐d‐glucopyranoside as starting materials, with 23 steps for the longest linear route. The l‐idose‐containing GH fragment was obtained by a short and straightforward synthesis whereby a 4,6‐cyclic‐acetal‐protected l‐idosyl thioglycoside bearing a C2‐nonparticipating group was used as the α‐selective glycosyl donor. The novel l‐idose donor was prepared with high chemo‐ and stereoselectivity by hydroboration–oxidation‐based C5 epimerization starting from an orthogonally protected α‐thioglucoside. The assembly of the pentasaccharide backbone was achieved by an F+GH and DE+FGH coupling sequence with full stereoselectivity in each glycosylation step.