Structure-activity relationship in PAF-acether. 4. Synthesis and biological activities of carboxylate isosteres.

The synthesis and biological characterization of some 3-carboxylate isosteres of PAF-acether structurally modified in positions 1 (ether, carbamate), 2 (acetoyl, ethoxy), and 3 (chain length and polar head group) are reported. All derivatives present antagonist activities against PAF-acether-induced effects in vitro (platelet aggregation) and in vivo (bronchoconstriction and thrombocytopenia in guinea pig and, to a lesser extent, hypotension in rat). The functional modifications presented here do not modify dramatically the potency of antagonist activities, and there is no enantioselectivity.

Radio-labelling of 1-O-alkyl, 2-O-acetyl, sn-glycero-3-phosphorylcholine, 1-O-(9,10-di3H)-octadecyl PAF-acether.

3H-labelling of 1-3H-PAF-aceter was prepared by catalytic reduction of 1-O-(9,10)-octadecenyl-2-O-benzyl-sn-glyceryl-3-phosphorylcholine and then acetylated. 5 mumoles of this dehydro derivative dissolved in methanol was treated during 4 hours with tritium gas (80 Ci) and compressed until 1.1 bar by an automatic tritium transfer unit [1].

New total synthesis and high resolution 1H NMR spectrum of platelet-activating factor, its enantiomer and racemic mixtures.

A new method of synthesis of octadecyl platelet-activating factor (PAF; 1-O-octadecyl 2-O-acetyl sn-glycero-3-phosphorylcholine) is described. Its advantage is to proceed by way of the 'lyso-PAF' which may be substituted by various groups, while avoiding the inconveniences of the total synthesis already described. Moreover, the intermediates in synthesis are easier to purify, with better yields.