Hansen, SU, Miller, GJ ORCID: https://orcid.org/0000-0001-6533-3306, Barath, M, Broberg, KR, Avizienyte, E, Helliwell, M, Raftery, J, Jayson, GC and Gardiner, JM (2012) Synthesis and Scalable Conversion of l-Iduronamides to Heparin-Related Di- and Tetrasaccharides. Journal Of Organic Chemistry, 77 (18). 7823 -7843.

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Abstract

A diastereomerically pure cyanohydrin, preparable on kilogram scale, is efficiently converted in one step into a novel l-iduronamide. A new regioselective acylation of this iduronamide and a new mild amide hydrolysis method mediated by amyl nitrite enables short, scalable syntheses of an l-iduronate diacetate C-4 acceptor, and also l-iduronate C-4 acceptor thioglycosides. Efficient conversions of these to a range of heparin-related gluco-ido disaccharide building blocks (various C-4 protection options) including efficient multigram access to key heparin-building block ido-thioglycoside donors are described. A 1-OAc disaccharide is converted into a heparin-related tetrasaccharide, via divergence to both acceptor and donor disaccharides. X-ray and NMR data of the 1,2-diacetyl iduronate methyl ester and the analogous iduronamide show that while both adopt 1C4 conformations in solution, the iduronate ester adopts the 4C1 conformation in solid state. An X-ray structure is also reported for the novel, 4C1-conformationally locked bicyclic 1,6-anhydro iduronate lactone along with an X-ray structures of a novel distorted 4C1 iduronate 4,6-lactone. Deuterium labeling also provides mechanistic insight into the formation of lactone products during the novel amyl nitrite-mediated hydrolysis of iduronamide into the parent iduronic acid functionality.

Item Type: Article
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Natural Sciences > School of Physical and Geographical Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 26 Nov 2015 09:08
Last Modified: 30 May 2019 13:44
URI: http://eprints.keele.ac.uk/id/eprint/1226

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