Systematic studies toward the synthesis of d -galactosamine-containing coumarin glycosides †

Wootton, Hannah S.; Miller, Gavin J.

Abstract

An O-glycosylation method for accessing coumarin glycosides is presented. We report the reaction of 6,8-difluoro-7-hydroxy-4-methylcoumarin and 4-methylumbelliferone with a variety of glycosyl imidate donors using BF3·Et2O as activator to access a series of coumarin glycosides in 64%−76% isolated yields. Several reaction parameters are evaluated including promotors, temperature and reagent equivalents. Following initial methodology development using simple d-glucose donors, d-galactosamino mono- and disaccharides are explored as substrates, showcasing applicability towards late-stage transformation of biologically relevant chondroitin sulfate glycosides. Glycosylation diastereoselectivity trends were also considered, proposing that the identity of the d-galactosamino N-protecting group and the coumarin acceptor contribute to observed anomeric product ratios. This methodology provides a convenient access to d-galactosamino-coumarin glycoconjugates and provides a benchmark for the development of related systems for biological evaluation.

Citation

Wootton, H. S., & Miller, G. J. (2025). Systematic studies toward the synthesis of d -galactosamine-containing coumarin glycosides †. Organic and Biomolecular Chemistry, https://doi.org/10.1039/d5ob00746a

• Journal Article Type: Article
• Acceptance Date: May 23, 2025
• Online Publication Date: May 23, 2025
• Publication Date: May 23, 2025
• Deposit Date: Jun 2, 2025
• Publicly Available Date: Jun 2, 2025
• Journal: Organic & Biomolecular Chemistry
• Print ISSN: 1477-0520
• Electronic ISSN: 1477-0539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1039/d5ob00746a
• Public URL: https://keele-repository.worktribe.com/output/1242525
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2025/ob/d5ob00746a