Synthesis of optically active ferrocene-containing platensimycin derivatives with a C6-C7 substitution pattern

Malay Patra, Gilles Gasser, Michaela Wenzel, Klaus Merz, Julia E. Bandow, Nils Metzler-Nolte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Concurrently with the emergence of purely organic derivatives of the naturally occurring antibiotic platensimycin (1a), herein, we describe the design, synthesis and biological evaluation of both the enantiomers of a C6-C7 ferrocene-fused platensimycin derivative 2b. (S,SP)- and (R,R P)-2b were prepared in nine steps starting from commercially available 4-ferrocenyl-4-oxobutyric acid via highly diastereoselective Michael additions of optically active planar-chiral ferrocene-fused cyclohexanone derivatives (5) with acrylate ester as the key step. Manual superimposition of (S,SP)-2b on platensimycin bound to the active site of its target enzyme FabF suggests that the former fits nicely in the active site and the C6-C7-fused ferrocene occupies a pocket similarly to the C8-C9-fused tetracyclic cage of 1a. Antimicrobial activities of (S,SP)- and (R,R P)-2b were tested against various Gram-positive and Gram-negative bacterial strains. An efficient synthetic route to optically active planar chiral ferrocene-containing bioorganometallics (2b) inspired by the antibiotic platensimycin lead structure has been developed. The absolute configurations were confirmed by X-ray crystallography. Docking experiments with (S,S P)-2b showed the existence of a pocket for the ferrocene fused at C6-C7 position of the cyclohexenone moiety. Compounds 2b represent a new family of compounds with an as yet unexplored substitution pattern compared to the reported purely organic analogues of platensimycin.

Original languageEnglish
Pages (from-to)3295-3302
Number of pages8
JournalEuropean Journal of Inorganic Chemistry
Issue number22
StatePublished - Aug 2011
Externally publishedYes


  • Antibacterial agents
  • Bioinorganic chemistry
  • Michael addition
  • Planar chiral ferrocene
  • Platensimycin
  • Sandwich complexes


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