The synthesis of new ketophosphonate isosteres of biosynthetic precursors of ether glycerophospholipids resistant to phospholipase C is described following two routes depending on whether the alkoxy chain is introduced before or after the phosphonic moiety. The common intermediates are ketophosphonic acids: better yields were obtained by attaching the n-octadecyl chain to epichlorohydrin, opening and oxidation, blockage of the resulting ketone as the chlorohydrazone, followed by an Arbuzov reaction or by azoene formation and Michael addition. These ketophosphonates differing in chain length in position 3 exhibit potent agonistic activities on rabbit platelets which increase with the number of methylene groups between the phosphonate and the ammonium moieties.