title: Synthesis of Fondaparinux: modular synthesis investigation for heparin synthesis.
abstract: 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 α-selectivity, while L-idopyranosyl trichloroacetimidate resulted in poor α/β selectivity. A practical synthesis of key intermediate 1,6-anhydro-L-idopyranose 17 by H(+)/β-CD catalyst was developed.
authors.affiliation: State Key Laboratory of New Drugs & Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, 1111 Zhongshanbeiyi Road, Shanghai 200437, China. linfeng@sioc.ac.cn
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.forename: Gaoyan
authors.initials: G
authors.lastname: Lian
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis*; D002240:Carbohydrate Sequence; D000077425:Fondaparinux; D005947:Glucose / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry; D006031:Glycosylation; D006493:Heparin / Q000138:chemical synthesis*; D006601:Hexoses / Q000737:chemistry; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000138:chemical synthesis*
chemical_list: D000925:Anticoagulants; D006027:Glycosides; D006601:Hexoses; D011134:Polysaccharides; C010997:idose; D006493:Heparin; D005947:Glucose; D000077425:Fondaparinux