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Synthesis and Biological Evaluation of Ferrocene-Containing Bioorganometallics Inspired by the Antibiotic Platensimycin Lead Structure

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posted on 11.10.2010, 00:00 authored by Malay Patra, Gilles Gasser, Michaela Wenzel, Klaus Merz, Julia E. Bandow, Nils Metzler-Nolte
The recent discovery of the natural product platensimycin (1) as a new antibiotic lead structure has triggered the synthesis of numerous organic derivatives for structure−activity relationships (SAR) in order to improve the poor in vivo efficacy of 1. The synthesis, characterization, and biological evaluation of the first four ferrocene-containing bioorganometallic compounds based on the platensimycin lead structure are reported herein, namely 3-(4,4-diferrocenoylpentanamido)-2,4-dihydroxybenzoic acid (2), 3-(4,4-diferrocenoylbutanamido)-2,4-dihydroxybenzoic acid (3), 3-{4-(acetylferrocenoyl)butanamido}-2,4-dihydroxybenzoic acid (4), and 3-(4-ferrocenoylbutanamido)-2,4-dihydroxybenzoic acid (5). All new compounds were unambiguously characterized by all common analytical methods, including 1H and 13C NMR, mass spectrometry, IR spectroscopy, and elemental analysis. Furthermore, the single-crystal X-ray structures of methyl 4,4-diferrocenoylbutanoate (9), methyl 4,4-diferrocenoylpentanoate (10), 4,4-diferrocenoylpentanoic acid (14), 4,4-diferrocenoylbutanoic acid (15), and 4-(acetylferrocenoyl)butanoic acid (16) were also determined. Among 25 and their intermediate carboxylic acids tested, only 3 was found to inhibit selectively the growth of S. aureus Mu50 strain (VISA) at a minimum inhibitory concentration (MIC) value of 128 μg/mL.