title: Planar chiral (η6-arene)Cr(CO)3 containing carboxylic acid derivatives: synthesis and use in the preparation of organometallic analogues of the antibiotic platensimycin.
abstract: With more and more organometallic compounds receiving attention for applications in medicinal organometallic chemistry, the need arises for stereoselective syntheses of more complicated structures containing organometallic moieties, for example as isosteric substitutes for organic drug candidates. Herein, the synthesis and characterization of both diastereomers of a planar chiral (η(6)-arene)Cr(CO)(3) containing carboxylic acid derivative, namely, 3-{η(6)-(1, 2, 3, 4-tetrahydro-1-endo/exo-methyl-2-oxonaphthalen-1-yl)-tricarbonylchromium(0)}propanoic acid (7 and 8) is reported. The molecular structures of both were confirmed by single crystal X-ray diffraction. The degree of diastereoselectivity in Cr(CO)(3) complexation with methyl/tert-butyl-3-(1,2,3,4-tetrahydro-1-methyl-2-oxonaphthalen-1-yl)propanoate (4a/4b) vs. the Michael addition of methyl/tert-butyl acrylate to (η(6)-1-methyl-2-tetralone)Cr(CO)(3) (9) was also examined. In the latter case the alkylation was found to be completely diastereoselective and gave methyl/tert-butyl-3-{η(6)-(1, 2, 3, 4-tetrahydro-1-endo-methyl-2-oxonaphthalen-1-yl)-tricarbonylchromium (0)}propanoate (5a and 5b) in excellent yield. Both the carboxylic acids 7 and 8 were coupled with the aminoresorcyclic acid core to achieve diastereomeric bioorganometallics 15a and 15b based on the naturally occurring antibiotic platensimycin lead structure (1a, see Fig. 1). The newly synthesized bioorganometallics were tested against various Gram-positive and Gram-negative bacterial strains but show no promising antibacterial activity.
authors.affiliation: Lehrstuhl für Anorganische Chemie I, Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Universitätsstr., 150, 44801, Bochum, Germany.
authors.forename: Malay
authors.initials: M
authors.lastname: Patra
authors.forename: Klaus
authors.initials: K
authors.lastname: Merz
authors.forename: Nils
authors.initials: N
authors.lastname: Metzler-Nolte
mesh_terms: D000218:Adamantane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D062365:Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry*; D002857:Chromium / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D062365:Aminobenzoates; D000813:Anilides; D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D056831:Coordination Complexes; D009942:Organometallic Compounds; D002857:Chromium; D000218:Adamantane; C510909:platensimycin