Enantioselective synthesis of ferrocenyl nucleoside analogues with apoptosis-inducing activity.
[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.
James
Philippe
P
Institute of Organic Chemistry, University of Cologne, Köln, Germany.
Neudörfl
Jörg
J
Eissmann
Moritz
M
Jesse
Patrick
P
Prokop
Aram
A
Schmalz
Hans-Günther
HG
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D009705:Nucleosides