Scalable Synthesis of <scp>l</scp>-Iduronic Acid Derivatives via Stereocontrolled Cyanohydrin Reaction for Synthesis of Heparin-Related Disaccharides

Abstract

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.