A Modular Strategy Toward the Synthesis of Heparin-like Oligosaccharides Using Monomeric Building Blocks in a Sequential Glycosylation Strategy

• Published in: Journal of the American Chemical Society Vol. 127; no. 11; pp. 3767 - 3773
• Main Authors: Codée, Jeroen D. C, Stubba, Bas, Schiattarella, Marialuisa, Overkleeft, Herman S, van Boeckel, Constant A. A, van Boom, Jacques H, van der Marel, Gijsbert A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 23.03.2005; Amer Chemical Soc
• Subjects: Carbohydrate Sequence; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Multidisciplinary; Exact sciences and technology; Glycosylation; Heparin - chemical synthesis; Molecular Sequence Data; Oligosaccharides - chemical synthesis; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Uronic Acids - chemical synthesis; Uronic Acids - chemistry; THIOGLYCOSIDES; L-IDURONIC ACID; PENTASACCHARIDE; FRAGMENTS; SULFATE; HIGH-AFFINITY; GLYCOSAMINO GLYCAN STRUCTURE; ANTITHROMBIN; INTERMOLECULAR AGLYCON TRANSFER; EFFICIENT; Stereoselectivity; Organic synthesis; Glycosaminoglycan; Heparitin sulfate; Glycosylation; Oligosaccharide
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja045613g

A novel flexible assembly strategy is described for the modular synthesis of heparin and heparan sulfates. The reported strategy uses monomeric building bocks to construct the oligosaccharide chain to attain a maximum degree of flexibility. In the assembly, 1-hydroxyl glucosazido- and 1-thio uronic acid donors are combined in a sequential glycosylation protocol using sulfonium triflate activator systems. The key 1-thio uronic acids were obtained in an efficient manner from diacetone glucose employing a chemo- and regioselective oxidation of partially protected glucose and idose thioglycosides.