Heparin/heparan sulphates (H/HS) are linear glycosaminoglycan (GAG) polysaccharides which play diverse critical cell-surface roles, including regulating many growth factors, evidence implicating L-iduronic containing domains and the number/location of sulfation as factors mediating effects. The complex heterogeneity of natural H/HS oligosaccharides necessitates synthesis to address a diversity of structurally-defined sequences. To date, synthesis of longer bioactive/bio-relevant oligosaccharides of 12-mer or above have seen only one example longer than 12 (a 16-mer fragment1b) and at the 12-mer length, syntheses reported have been at the multi-mg level. Here we will describe the first gram-scale heparin-like dodecasaccharide syntheses2b,c (enabled by new scalable iduronic acid synthesis2a).
Secondly, we will describe a new strategy that has delivered chain-extension of heparin-like oligosaccharides affording a series of the longest heparin-like oligosaccharides yet described up to 36-mer.2c This doubles any previous length of synthetic heparin-like oligoaccharides yet reported, and we believe also provides one of the longest examples of linear synthetic oligosaccharide yet prepared.
