The synthesis of the five-membered cyclic phosphorodiamidic-acid derivatives 10 and 11 as well as the preparation of the six-membered cyclic phosphates 18, 19,22-25, and phosphoramidates 27-32 is described. The effects of these conformationally restricted platelet-activating factor analogs on rabbit platelet aggregation are briefly discussed. The 2-0x0-I ,3,2-dioxaphosphorinanes 19,25, and 30 were found to be equally potent platelet-activating factor antagonists as the known thiazolium salt 33.
') The amino alcohol 6 was prepared from (S)-1-0-octadecyl-glycerol[27] in three steps: i ) TsC1, pyridine; ii) NaN,, DMF; iii) H2, Pd/C, THF. We thank Dr. R. Burner and Mr. G. Hirth for providing us with the experimental details of this reaction sequence [28]. c 1 (7)*) in the presence of Et,N led to the formation of the two diastereoisomers 8 (27 %) and 9 (26 YO), which could be easily separated by chromatography. Assignment of configuration at the P-atom is based on the observation that a P=O bond exhibits a deshielding effect on the protons in a 1,3-cis-relationship [30] as indicated in formula 9. Thus, the 'H-NMR signal for H-C(5) in 9 appears at 4.65 ppm, while the corresponding proton in 8 resonates at 4.53 ppm. *) This compound was available by heating 2-aminoethyl bromide hydrobromide in POC1, according to a protocol developed for the preparation of the corresponding 2-chloroethyl derivative [29].