Synthesis and in vivo evaluation of 4-deoxy-4,4-difluoro-KRN7000.
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.
Leung
Leo
L
School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.
Tomassi
Cyrille
C
Van Beneden
Katrien
K
Decruy
Tine
T
Elewaut
Dirk
D
Elliott
Tim
T
Al-Shamkhani
Aymen
A
Ottensmeier
Christian
C
Van Calenbergh
Serge
S
Werner
Joern
J
Williams
Tony
T
Linclau
Bruno
B
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
C533292:4-deoxy-4,4-difluoro-KRN7000; D016207:Cytokines; D005699:Galactosylceramides; D001554:Benzene; C103873:KRN 7000