CHIRAL FORMS OF ',4'-DIFLUOROBIPHENYL-4-YL)-2-METHYL-4-OXOBUTANOIC ACID (FLOBUFEN) AND ITS METABOLITE - SYNTHESIS AND BASIC BIOLOGICAL PROPERTIES

',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (1, flobufen) is subjected to clinical testing in the treatment of rheumatoid arthri tis. Owing to the occurrence of a centre of chirality, the compound ex ists in two enantiomers, and its major human metabolite, vb. -difluoro biphenyl-4-yl)-4-hydroxy-2-methylbutanoic acid isolated in the lactone form (2), possesses two chiral centres, making possible the existence of four stereoisomers. All of the optical isomers of the substances 1 and 2 were prepared. For flobufen (1), the racemate was separated int o the stereoisomers by using the salts 3 with R-(+)- or S-(-)-1-phenyl ethylamine. The pairs of stereoisomers of 2, obtained by reduction of R-(+)-flobufen or the S-(-)-enantiomer, were separated by column chrom atography. The physico-chemical parameters of the optical isomers were determined and some biological activities were evaluated in both in v itro and in vivo models.