Kim Messer

The absolute configuration of (+)-isoshinanolone and in situ LC-CD analysis of its stereoisomers from crude extracts

The absolute configuration of (+)-isoshinanolone, a wide-spread acetogenic metabolite from higher plants, has been determined by X-ray structure analysis of its new dibromide; accordingly, this natural tetralone is 3R,4R-configured, in agreement with previous degradative results. In addition, a first chiroptical on-line stereoanalysis for isoshinanolones is presented, i.a. by HPLC on a chiral phase coupled to CD spectroscopy, giving pure CD spectra of all of the four stereoisomers of isoshinanolone directly from stereoisomeric mixtures.

Habropetaline A, an antimalarial naphthylisoquinoline alkaloid from Triphyophyllum peltatum.

The isolation, structural elucidation, and antiprotozoal activities of habropetaline A, a novel naphthylisoquinoline alkaloid from Triphyophyllum peltatum, are described. This alkaloid had previously only been identified on line, by the LC-MS/MS-NMR-CD triad, in the crude extract of the rare and difficult-to-provide related plant species Habropetalum dawei, whose small quantities available had not permitted to isolate the compound. As predicted by quantitative structure-activity relationship (QSAR) investigations, habropetaline A exhibits strong antimalarial activity against Plasmodium falciparum, while it is inactive against other protozoal pathogens (Trypanosoma brucei rhodesience, T. cruzi, and Leishmania donovani).

Acridizinium Salts as a Novel Class of DNA-binding and Site-selective DNA-photodamaging Chromophores¶

Abstract It was demonstrated that the interaction of the aminoacridizinium salts 2a–2d with DNA depends on the substitution pattern of the chromophore. Spectrophotometric and fluorometric titrations of the acridizinium salts 2a–2d with natural and synthetic polynucleotides reveal that the degree of interaction of the acridizinium salts 2a–2d with the nucleic acid differs significantly. The binding mode of the dyes with DNA was evaluated by circular dichroism and linear dichroism spectroscopy and compared with the parent system 2c. Whereas the 9-aminoacridizinium (2a) mainly intercalates into DNA, the salts 2b–c show a higher degree of association to the DNA backbone. The intercalated aminoacridizinium 2a caused few strand breaks upon UVA exposure, whereas the salts 2b–2d exhibit relatively efficient DNA-damaging properties. All acridizinium salts showed a sequence-selective strand cleavage for guanine-rich DNA regions.

Cis- and trans-isoshinanolone from Dioncophyllum thollonii: absolute configuration of two `known', wide-spread natural products

Abstract From the rare West African liana, Dioncophyllum thollonii (Dioncophyllaceae), the known acetogenic tetralones, cis - and trans -isoshinanolone, were isolated. Exemplarily on this material, a new ruthenium-catalyzed oxidative degradation procedure, related to the well-established stereoanalysis of 1,3-dimethyltetrahydroisoquinolines, was elaborated. The method allows to unambiguously attribute the absolute configuration of these natural products, which likewise occur in several other plant species. For the rapid discrimination between the four possible stereoisomeric forms of isoshinanolone (i.e. the cis - and trans -diastereomers and their enantiomers), an HPLC-analytical procedure on a chiral stationary phase has been developed.

Elucidation of the absolute configuration of knipholone and knipholone anthrone by quantum chemical CD calculations

The absolute configuration of knipholone, an axially chiral phenylanthraquinone from Kriphofia, Bulbine, and Bulbinella species, has been established as M by quantum chemical CD calculations. For further evidence, the absolute stereostructure of the related compound knipholone, which has a significantly different chromophor, was likewise elucidated. The fact that both natural biaryls compounds were independently attributed the same absolute configuration, underlines the reliability of the results and the value of the applied method.

Acetogenic isoquinoline alkaloids: CXXI. Use of on-line high-performance liquid chromatography–nuclear magnetic resonance spectrometry coupling in phytochemical screening studies: rapid identification of metabolites in Dioncophyllum thollonii

Abstract Exemplarily for a root extract of the West African liana Dioncophyllum thollonii a strategy for the rapid identification of secondary metabolites in plant extracts is presented, based upon on-line coupling of high-performance liquid chromatography with nuclear magnetic resonance detection. For a first overview, an on-flow experiment was performed, which allowed the identification of the naphthylisoquinoline alkaloid dioncophylline A. A second alkaloid, 5′-O-demethyldioncophylline A, was identified by subsequent application of stop-flow two-dimensional HPLC–NMR ROESY experiments. In the case of coeluting compounds, the design of appropriate time-slice experiments allowed the characterization of the diastereomeric tetralones trans- and cis-isoshinanolone. Thus, through consequent use of all different experimental modes available in HPLC–NMR, a phytochemical screening of plant extracts can be realized in a fast and reliable way. The NMR detection allows the characterization of diastereomeric compounds even in the case of far-reaching chromatographic coelution.

Jozipeltine A, a Novel, Unnatural Dimer of the Highly Hydroxylated Naphthylisoquinoline Alkaloid Dioncopeltine A

Abstract The synthesis of jozipeltine A (5), the 6′-coupled constitutionally symmetric dimer of the highly antimalarial naphthylisoquinoline alkaloid dioncopeltine A (4), is described. After selective protection of two of the four OH- and NH-functionalities of 4, the coupling succeeds oxidatively, with Ag2O as the reagent. Deprotection gives the target molecule 5, in only three steps from 4. Jozipeltine A is the first naphthylisoquinoline dimer with oxygen functions in the side chain of the naphthalene part. Investigations on its antiplasmodial and antiviral activities provide valuable insight into structure–activity relationships within this promising class of bioactive quateraryls.

Synthesis and Investigation of the DNA-Binding and DNA-Photodamaging Properties of Indolo[2,3-b]quinolizinium Bromide

The readily available cationic dye 3-Br binds to DNA as was shown by UV, fluorescence and CD spectroscopy. The electronic spectra of the quinolizinium salt 3 exhibit significant bathochromic shifts and a decrease of the absorbance and emission intensity on addition of calf thymus DNA. Moreover, fluorometric titration of [poly(dCdG)]2 with salt 3 resulted in a significant decrease of the emission intensity, whereas addition of [poly(dAdT)]2 led only to a marginal perturbation of the emission spectrum. Analysis of the binding constants with the different polynucleotides revealed that quinolizinium 3-Br binds preferentially to GC base pairs. Irradiation of DNA in the presence of quinolizinium 3-Br resulted in efficient single-strand cleavage of the nucleic acid.