Phosphatidylinositol analogues, inhibitors of phosphatidylinositol specific phospholipase C

A process for preparing phosphatidylinositol analogue inhibitors of phosphatidylinositol-specific phospholipase C having the following general formula (I):

• ##STR24## wherein X is S or O, and R has one of the following meanings:
• 1) a branched or linear alkyl radical selected from the group consisting of octyl, tetradecyl, hexadecyl, octadecyl, and eicosyl;
• 2) an arylalkyl radical selected from the group consisting of benzyl, phenylethyl, naphthylethyl, phenylpropyl, and phenylhexyl;
• 3) 2,3 diacyloxypropyl:
• ##STR25## wherein R.sub.6 is a saturated or unsaturated acyl radical selected from the group consisting of oleyl, linoleyl, linolenyl, myristoyl, and lauroyl;
• 4) 2,3 dialkyloxypropyl:
• ##STR26## wherein R.sub.7 is a saturated or unsaturated alkyl radical selected from the group consisting of stearyl, palmityl, oleyl, myristyl, and cetyl;
• 5) 2,3 alkylacyloxypropyl ##STR27## wherein R.sub.8 is a saturated or unsaturated alkyl radical selected from the group consisting of stearyl, palmityl, oleyl, myristyl, and cetyl and R.sub.9 is acetyl;
• 6) an alkyl radical containing a carbonyl group of formula:
• R.sub.10 --COZ(CH.sub.2).sub.n --
• wherein R.sub.10 has the same meaning as R at item 1, Z=O, NH, and n ranges from 2 to 6;
• 7) an alkyl radical containing a carbonyl group of formula:
• R.sub.10 --YCO(CH.sub.2).sub.m --
• wherein R.sub.10 has the same meaning as R at item 5, Y=O, NH, S and m ranges from 1 to 6;
• wherein when X=S, said process comprises:
• (a) transesterifying by treatment with trimethylsilylbromide a diethylphosphothiolate having the general formula:
• ##STR28## (b) treating the transesterified product of step (a) with myoinositol protected at hydroxyl groups 2, 3, 4, 5 and 6 in the presence of a condensing agent;
• and
• (c) removing the protecting groups of the compound produced in step (b) and thereby restoring the hydroxyl groups 2, 3, 4, 5 and 6;
• and wherein when X=O, said process comprises:
• (a) transesterifying by treatment with trimethylsilylbromide a phosphoric triester having the formula:
• ##STR29## (b) treating the transesterified product of step (a) with myoinositol protected at hydroxyl groups 2, 3, 4, 5 and
• (c) removing the protecting groups of the compound produced in step (b) and thereby restoring the hydroxyl groups 2, 3, 4, 5 and 6.