title: Synthesis and in vivo evaluation of 4-deoxy-4,4-difluoro-KRN7000.
abstract: The synthesis of 4-deoxy-4,4-difluoro-KRN7000 starting from phytosphingosine is described. Key steps include a regioselective benzylation of azidophytosphingosine and a deoxofluor-mediated fluorination of the corresponding 4-ketone. This fluorination failed completely when the adjacent 3-OH was protected as benzyl ether but proceeded well when a benzoyl group was used. The biological evaluation reveals a bias toward Th1 cytokine induction upon Natural Killer T cell activation.
authors.affiliation: School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.
authors.forename: Leo
authors.initials: L
authors.lastname: Leung
authors.forename: Cyrille
authors.initials: C
authors.lastname: Tomassi
authors.forename: Katrien
authors.initials: K
authors.lastname: Van Beneden
authors.forename: Tine
authors.initials: T
authors.lastname: Decruy
authors.forename: Dirk
authors.initials: D
authors.lastname: Elewaut
authors.forename: Tim
authors.initials: T
authors.lastname: Elliott
authors.forename: Aymen
authors.initials: A
authors.lastname: Al-Shamkhani
authors.forename: Christian
authors.initials: C
authors.lastname: Ottensmeier
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
authors.forename: Joern
authors.initials: J
authors.lastname: Werner
authors.forename: Tony
authors.initials: T
authors.lastname: Williams
authors.forename: Bruno
authors.initials: B
authors.lastname: Linclau
mesh_terms: D000818:Animals; D001554:Benzene / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure
chemical_list: C533292:4-deoxy-4,4-difluoro-KRN7000; D016207:Cytokines; D005699:Galactosylceramides; D001554:Benzene; C103873:KRN 7000