Synthesis of Fondaparinux: modular synthesis investigation for heparin synthesis

The anti-thromboembolic pentasaccharide Fondaparinux was synthesized in 36 steps for the longest linear route, with 0.017% overall yield from D-glucose. Only three kinds of protecting groups were used for hydroxyl protection, Bn, Ac, and Bz, to accomplish this complex synthesis without decreasing the synthetic efficiency. Three L-idopyranosyl donors were investigated. Thioethyl glycoside is an efficient donor for L-idopyranosyl glycosylation with full alpha-selectivity, while L-idopyranosyl trichloroacetimidate resulted in poor alpha/beta selectivity. A practical synthesis of key intermediate 1,6-anhydro-L-idopyranose 17 by H+/beta-CD catalyst was developed. (C) 2013 Elsevier Ltd. All rights reserved.