A facile synthesis of 1-O-alkyl-2-(R)-hydroxypropane-3-phosphonocholine (lyso-phosphono-platelet activating factor).
The synthesis of 1-O-alkyl-2-(R)-hydroxypropane-3-phosphonocholine is described. An efficient alkylation procedure using (NaH/DMSO) catalysis is also described and applied to the synthetic scheme. The key intermediate 1-O-alkyl-2-(R)-O-benzyl-3-bromopropane was phosphonylated using tris(methylsilyl)phosphite; the resulting phosphonic acid was coupled to choline using trichloroacetonitrile/pyridine or triisopropylbenzenesulfonyl chloride/pyridine followed by catalytic hydrogenation to yield 1-O-alkyl-2(R)-hydroxypropane-3-phosphonocholine.
Schmitt
J D
JD
Department of Biochemistry, Wake Forest University Medical Center, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1016.
Nixon
A B
AB
Emilsson
A
A
Daniel
L W
LW
Wykle
R L
RL
D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010739:Phospholipase D / Q000378:metabolism; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism
D007202:Indicators and Reagents; D010972:Platelet Activating Factor; C078791:1-O-hexadecyl-2-hydroxypropane-3-phosphonocholine; D010738:Type C Phospholipases; D010739:Phospholipase D