title: Synthesis of the heparin-based anticoagulant drug fondaparinux.
abstract: Fondaparinux, a synthetic pentasaccharide based on the heparin antithrombin-binding domain, is an approved clinical anticoagulant. Although it is a better and safer alternative to pharmaceutical heparins in many cases, its high cost, which results from the difficult and tedious synthesis, is a deterrent for its widespread use. The chemical synthesis of fondaparinux was achieved in an efficient and concise manner from commercially available D-glucosamine, diacetone α-D-glucose, and penta-O-acetyl-D-glucose. The method involves suitably functionalized building blocks that are readily accessible and employs shared intermediates and a series of one-pot reactions that considerably reduce the synthetic effort and improve the yield.
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Taipei 115 (Taiwan); Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 300 (Taiwan).
authors.forename: Cheng-Hsiu
authors.initials: CH
authors.lastname: Chang
authors.forename: Larry S
authors.initials: LS
authors.lastname: Lico
authors.forename: Teng-Yi
authors.initials: TY
authors.lastname: Huang
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Chi-Liang
authors.initials: CL
authors.lastname: Chang
authors.forename: Susan D
authors.initials: SD
authors.lastname: Arco
authors.forename: Shang-Cheng
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis* / Q000627:therapeutic use; D000077425:Fondaparinux; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux
keywords: anticoagulant; carbohydrates; heparin; one-pot reactions; total synthesis