Synthesis and biological activity of α-l-fucosyl ceramides, analogues of the potent agonist, α-d-galactosyl ceramide KRN7000

Natacha Veerapen, Faye Reddington, Gabriel Bricard, Steven A. Porcelli, Gurdyal S. Besra

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Several l-fucoglycolipids are associated with diseases such as cancer, cystic fibrosis and rheumatoid arthritis. Activation of iNKT cells is known to lead to the production of cytokines that can help alleviate or exacerbate these conditions. α-Galactosyl ceramide (α-GalCer) is a known agonist of iNKT cells and it is believed that its fucosyl counterpart might have similar immunogenic properties. We herein report the synthesis of α-l-fucosyl ceramide derivatives and describe their biological evaluation. The key challenge in the synthesis of the target molecules involved the stereoselective synthesis of the α-glycosidic linkage. Of the methods examined, the per-TMS-protected glycosyl iodide donor was completely α-selective, and could be scaled up to provide gram quantities of the azide precursor 11, from which a range of N-acylated α-l-fucosyl ceramides were readily obtained and evaluated for ex vivo expansion of human iNKT cells.

Original languageEnglish (US)
Pages (from-to)3223-3226
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number11
DOIs
StatePublished - Jun 1 2010

Keywords

  • Antigen
  • CD1d
  • Ceramide
  • Lipid
  • iNKT

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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