New synthesis of idraparinux, the non-glycosaminoglycan analogue of the antithrombin-binding domain of heparin

作者：Herczeg Mihaly; Mezo Erika; Eszenyi Daniel; Antus Sandor; Borbas Aniko^*

来源：Tetrahedron, 2014, 70(18): 2919-2927.

DOI：10.1016/j.tet.2014.03.033

• Anticoagulation
• Heparinoid pentasaccharide
• Glycosylation reactions
• Orthogonal protecting groups
• Multiple functionalization
• Uronic acids

Idraparinux, the fully O-sulfated, O-methylated, heparin-related pentasaccharide possessing selective factor Xa inhibitory activity, was prepared by a new synthetic pathway. This route was based on a [2+3] block synthesis utilizing a 6-O-silyl-protected L-idose-containing trisaccharide acceptor, which was glycosylated with a disaccharide donor containing a non-oxidized precursor of the glucuronic acid. The unique strategy of multiple functionalizations at pentasaccharide levels, involving triple methylation followed by oxidation of the glucose and the idose precursors into D-glucuronic and L-iduronic acids in one step, proved to be highly efficient, providing the target pentasaccharide through a 39-step synthesis starting from D-glucose and methyl alpha-D-glucopyranoside.

• 出版日期2014-5-6