title: Synthesis of L-iduronic acid derivatives via [3.2.1] and [2.2.2] L-iduronic lactones from bulk glucose-derived cyanohydrin hydrolysis: a reversible conformationally switched superdisarmed/rearmed lactone route to heparin disaccharides.
abstract: L-Idofuranoside cyanohydrin 1 is converted on large scale into a mixture of L-IdoA methyl pyranosides and furanosides, which is converged to provide short 2-step routes to bicyclic [3.2.1] or [2.2.2] L-iduronate lactones. The former is obtained via a 100 g scale synthesis of 3-OBn L-IdoA. A two-step conversion of this mixture provides either pure anomer of the novel [2.2.2] l-iduronate thioglycoside lactones. Both [3.2.1] and [2.2.2] lactones are converted into GlcN-IdoA heparin precursor disaccharides. The [2.2.2] lactone enables a scalable 3-step route from 1 to a new type of highly disarmed O-4 iduronate thioglycoside, which is an effective acceptor with glucoazide thioglycoside donors. The resulting new iduronic [2.2.2] lactone disaccharides are readily rearmed by mild methanolysis to provide GlcN-IdoA thiophenyl disaccharide donors, intercepting their established utility for the assembly of both heparin- and heparan sulfate-like oligosaccharides. The [2.2.2] lactonization acts as a conformational switch to superdisarm iduronate components, reversible by lactone ring opening. In addition, the separated 2,4-diacetates also provide short access to all four anomeric and ring size isomers of l-iduronic acid methyl glycosides, including the first syntheses of the parent idofuranosides. X-ray structures are reported for a [2.2.2] iduronate lactone and examples of both methyl L-idopyranoside and novel methyl-L-idofuranoside systems.
authors: †Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, U.K.
authors: Steen U
authors: SU
authors: Hansen
authors: †Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, U.K.
authors: Charlotte E
authors: CE
authors: Dalton
authors: †Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, U.K.
authors: Marek
authors: M
authors: Baráth
authors: †Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, U.K.
authors: Glenn
authors: G
authors: Kwan
authors: §The School of Chemistry, The University of Manchester, Manchester M13 9PL, U.K.
authors: James
authors: J
authors: Raftery
authors: ∥Institute of Cancer Sciences, Christie Hospital and University of Manchester, Wilmslow Road, Manchester M20 4BX, U.K.
authors: Gordon C
authors: GC
authors: Jayson
authors: †Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, U.K.|§The School of Chemistry, The University of Manchester, Manchester M13 9PL, U.K.
authors: Gavin J
authors: GJ
authors: Miller
authors: †Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, U.K.
authors: John M
authors: JM
authors: Gardiner
mesh_terms: D006493:Heparin / Q000031:analogs & derivatives* / Q000737:chemistry*; D006868:Hydrolysis; D007067:Iduronic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009570:Nitriles / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry*
chemical_list: D007783:Lactones; D009570:Nitriles; D009844:Oligosaccharides; C430593:cyanohydrin; D007067:Iduronic Acid; D006493:Heparin