Scalable synthesis of L-iduronic acid derivatives via stereocontrolled cyanohydrin reaction for synthesis of heparin-related disaccharides.
L-ido cyanohydrin 3 was prepared from diacetone-D-glucose in four steps and 76% overall yield and 90% de via cyanohydrin reaction of aldehyde 2. This process can be scaled to provide >1 mol of pure L-ido cyanohydrin 3. Cyanohydrin 3 was elaborated to 1,2-isopropylidine-protected L-ido nitrile (8), iduronic amide 9, and known carboxy ester 10. Coupling of 8 and 9 with glucosamine donors leads to new types (6-cyano and 6-carboxamide) of heparin-related disaccharides.
Hansen
Steen Uldall
SU
School of Chemistry and Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK. gardiner@manchester.ac.uk
Baráth
Marek
M
Salameh
Bader A B
BA
Pritchard
Robin G
RG
Stimpson
William T
WT
Gardiner
John M
JM
Jayson
Gordon C
GC
D000388:Air; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D007067:Iduronic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D007202:Indicators and Reagents / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013696:Temperature
D004187:Disaccharides; D007202:Indicators and Reagents; D009570:Nitriles; C430593:cyanohydrin; D007067:Iduronic Acid; D006493:Heparin