SYNTHETIC STUDY OF THE HIGHLY POTENT AND SELECTIVE ANTIPLATETLET ACTIVATING FACTOR THIAZOLIDIN-4-ONE AGENTS AND RELATED-COMPOUNDS

Stereoselective cycle-condensation of alpha-sulfanylcarboxylic acids ( or esters) 6 with N-methylarylimmines 7 afforded the title compounds, 2-arylthiazolidin-4-ones, some of which exhibit highly potent anti-PAF activity. The reaction without added catalyst gave predominantly cis products, however, when titanium(iv) isopropoxide was added as catalys t trans products were predominantly formed. Allylation of 3-methyl-2-( 3-pyridyl)thiazolidin-4-one 22 with allyl bromide using lithium amides gave the trans-5-allyl-2-(3-pyridyl)thiazolidin-4-one 23 with good se lectivity. To study the stereostructure-activity relationship, the fou r optically active isomers of 3,5-dimethyl-2-(3-pyridyl)thiazolidin-4- one 4 and orophenyl)-3-methyl-2-(3-pyridyl)thiazolidin-4-one 5 were sy nthesized. The absolute configurations of compounds 4 and 5 were deter mined by X-ray analyses and H-1 NMR measurements. Epimerization of the 5-position of compounds 4 and 5 was found to be effected by bases wit h high regioselectivity (>99%), which was checked by a cross-over expe riment using several optically active compounds.