Enantioselective Synthesis of Ferrocenyl Nucleoside Analogues with Apoptosis-Inducing Activity Academic Article uri icon

abstract

  • [reaction: see text] 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 (RCH(2)). Other important steps include a Dieckmann cyclization and the attachment of the nucleobase (NB) in an iron-assisted S(N)1 reaction. Some of the target compounds were shown to exhibit significant apoptosis-inducing activity (LD(50) = 10-20 microM) against tumor cells.

authors

  • James, Philippe
  • Neudörfl, Jörg
  • Eissmann, Moritz
  • Jesse, Patrick
  • Prokop, Aram
  • Schmalz, Hans-Günther

publication date

  • June 2006