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

Hansen, Steen U.; Dalton, Charlotte E.; Baráth, Marek; Kwan, Glenn; Raftery, James; Jayson, Gordon C.; Miller, Gavin J.; Gardiner, John M.

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.

Citation

Hansen, S. U., Dalton, C. E., Baráth, M., Kwan, G., Raftery, J., Jayson, G. C., …Gardiner, J. M. (2015). 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. Journal of Organic Chemistry, 80(8), 3777 -3789. https://doi.org/10.1021/jo502776f

• Journal Article Type: Article
• Acceptance Date: Feb 3, 2015
• Publication Date: Feb 3, 2015
• Journal: Journal Of Organic Chemistry
• Print ISSN: 0022-3263
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 80
• Issue: 8
• Pages: 3777 -3789
• DOI: https://doi.org/10.1021/jo502776f
• Publisher URL: http://dx.doi.org/10.1021/jo502776f