<scp>d</scp>-Glucuronate and <scp>d</scp>-Glucuronate Glycal Acceptors for the Scalable Synthesis of <scp>d</scp>-GlcN-α-1,4-<scp>d</scp>-GlcA Disaccharides and Modular Assembly of Heparan Sulfate

Abstract

High Resolution Image Download MS PowerPoint Slide Reported herein is a scalable chemical synthesis of disaccharide building blocks for heparan sulfate (HS) oligosaccharide assembly. The use of d -glucuronate-based acceptors for dehydrative glycosylation with d -glucosamine partners is explored, enabling diastereoselective synthesis of appropriately protected HS disaccharide building blocks ( d -GlcN-α-1,4- d -GlcA) on a multigram scale. Isolation and characterization of key donor (1,2 glycal)- and acceptor (ortho-ester, anhydro)-derived side products ensure methodology improvements to reduce their formation; protecting the d -glucuronate acceptor at the anomeric position with a para -methoxyphenyl unit proves optimal. We also introduce glycal uronate acceptors, showing them to be comparative in reactivity to their pyranuronate counterparts. Taken together, this gram-scale access offers the capability to explore the iterative assembly of defined HS sequences containing the d -GlcN-α-1,4- d -GlcA repeat, highlighted by completing this for two tetrasaccharide syntheses.