Enantioselective Synthesis of Ferrocenyl Nucleoside Analogues with Apoptosis-Inducing Activity

As a contribution to bioorganometallic chemistry, an enantioselective synthesis of novel carbocyclic nucleoside analogues with a ferroceno-cyclopentene backbone was developed. Diastereoselective cuprate 1,4-addition or Mukaiyama−Michael addition to a planar-chiral enoate (ethyl (E)-2-[2-methoxycarbonyl-ferrocenyl]-acrylate) allowed for the introduction of different side chains (RCH2). Other important steps include a Dieckmann cyclization and the attachment of the nucleobase (NB) in an iron-assisted SN1 reaction. Some of the target compounds were shown to exhibit significant apoptosis-inducing activity (LD50 = 10−20 μM) against tumor cells.