Synthesis of a heparan sulfate tetrasaccharide using automated glycan assembly †

Pongener, Imlirenla; Sletten, Eric T.; Danglad-Flores, José; Seeberger, Peter H.; Miller, Gavin J.

Abstract

Herein we utilise automated glycan assembly to complete solid-phase synthesis of defined heparan sulfate oligosaccharides, employing challenging d-glucuronate disaccharide donors. Using an orthogonally protected d-GlcN-α-d-GlcA donor, milligram-scale synthesis of a heparan sulfate tetrasaccharide is completed in 18% yield over five steps. Furthermore, orthogonal protecting groups enabled regiospecific on-resin 6-O-sulfation. This methodology provides an important benchmark for the rapid assembly of biologically relevant heparan sulfate sequences.

Citation

Pongener, I., Sletten, E. T., Danglad-Flores, J., Seeberger, P. H., & Miller, G. J. (in press). Synthesis of a heparan sulfate tetrasaccharide using automated glycan assembly †. Organic and Biomolecular Chemistry, https://doi.org/10.1039/d3ob01909h

• Journal Article Type: Article
• Acceptance Date: Jan 16, 2024
• Online Publication Date: Jan 24, 2024
• Deposit Date: Feb 5, 2024
• Publicly Available Date: Feb 5, 2024
• Journal: Organic & Biomolecular Chemistry
• Print ISSN: 1477-0520
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1039/d3ob01909h
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2024/ob/d3ob01909h