ENANTIOSELECTIVE SYNTHESIS OF FERROCENE ANALOGS OF HEXESTROL AND ESTRADIOL - RECOGNITION TOWARDS ESTRADIOL RECEPTORS

We describe herein the synthesis of the first non-steroidal ferrocene analogs of estradiol, in which the five-membered ring (D) is replaced by a cyclopentadienyl ligand. The control of the three chiral elements for ydroxymethyl)ferrocenyl)-4-(4-hydroxyphenyl)hexane (4a,4b) and (( 2-methyl)ferrocenyl)-4-(4-hydroxyphenyl)-hexane: (5a,5b) was achieved by asymmetric cyclopalladation of N,N-dimethylaminomethylferrocene. Th e relative configurations were unambiguously determined from X-ray str ucture analyses on the racemic materials at each key step of the synth esis. All the ferrocene derivatives synthesized are recognized by the estradiol receptors. The best results are obtained for molecules posse ssing the same ethyl group disposition as that found in meso-hexestrol .