Making the longest sugars: a chemical synthesis of heparin-related [4]n oligosaccharides from 16-mer to 40-mer. Issue 11 (6th August 2015)

• Record Type: Journal Article
• Authors: Hansen, Steen U.; Miller, Gavin J.; Cliff, Matthew J.; Jayson, Gordon C.; Gardiner, John M.
• Is Part Of: Chemical science. Volume 6:Issue 11(2015:Nov.)
• Page Start: 6158
• Page End: 6164
• Publication Date: 2015-08-06
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5sc02091c
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Synthesis of the longest heparin-related oligosaccharide backbones is enabled by efficient iterative [4] n -mer homologations via solution-phase synthesis. Pure-Shift HSQC NMR provides a dramatic improvement in anomeric signal resolution. Abstract : The chemical synthesis of long oligosaccharides remains a major challenge. In particular, the synthesis of glycosaminoglycan (GAG) oligosaccharides belonging to the heparin and heparan sulfate (H/HS) family has been a high profile target, particularly with respect to the longer heparanome. Herein we describe a synthesis of the longest heparin-related oligosaccharide to date and concurrently provide an entry to the longest synthetic oligosaccharides of any type yet reported. Specifically, the iterative construction of a series of [4] n -mer heparin-backbone oligosaccharides ranging from 16-mer through to the 40-mer in length is described. This demonstrates for the first time the viability of generating long sequence heparanoids by chemical synthesis, via practical solution-phase synthesis. Pure-Shift HSQC NMR provides a dramatic improvement in anomeric signal resolution, allowing full resolution of all 12 anomeric protons and extrapolation to support anomeric integrity of the longer species. A chemically pure 6- O -desfulfated GlcNS-IdoAS icosasaccharide (20-mer) represents the longest pure synthetic heparin-like oligosaccharide.