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 3-((2-hydroxymethyl)ferrocenyl)-4-(4-hydroxyphenyl)hexane (4a,4b) and 3-((2-methyl)ferrocenyl)-4-(4-hydroxyphenyl)-hexane: (5a,5b) was achieved by asymmetric cyclopalladation of N,N-dimethylaminomethylferrocene. The relative configurations were unambiguously determined from X-ray structure analyses on the racemic materials at each key step of the synthesis. All the ferrocene derivatives synthesized are recognized by the estradiol receptors. The best results are obtained for molecules possessing the same ethyl group disposition as that found in meso-hexestrol.