title: Total synthesis of α-1C-galactosylceramide, an immunostimulatory C-glycosphingolipid, and confirmation of the stereochemistry in the first-generation synthesis.
abstract: A nonisosteric α-C-glycoside analogue of KRN7000 (α-1C-GalCer, 1) was reported to induce a selective type of cytokine release in human invariant natural killer cells in vitro. We report here a very concise synthetic route to 1 and its analogue 1'. The key steps include olefin cross-metathesis, Sharpless asymmetric epoxidation, and epoxide opening by NaN(3)/NH(4)Cl. Inversion of configuration at the amide-bearing carbon in the phytosphingosine backbone constructed by epoxide opening in our previous synthesis of 1 was verified, indicating that remote group participation is not involved during the epoxide-opening reaction.
authors.affiliation: Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, New York 11367-1597, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Hoe-Sup
authors.initials: HS
authors.lastname: Byun
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology*; D000475:Alkenes / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D005699:Galactosylceramides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006028:Glycosphingolipids / Q000737:chemistry*; D006801:Humans; D007114:Immunization; D008968:Molecular Conformation; D015394:Molecular Structure; D055611:Natural Killer T-Cells / Q000737:chemistry / Q000187:drug effects*; D013237:Stereoisomerism
chemical_list: D000276:Adjuvants, Immunologic; D000475:Alkenes; D004852:Epoxy Compounds; D005699:Galactosylceramides; D006028:Glycosphingolipids; C493154:alpha-galactosylceramide; C103873:KRN 7000