Biaryls in Nature: A Multi-Facetted Class of Stereochemically, Biosynthetically, and Pharmacologically Intriguing Secondary Metabolites

Bringmann, Gerhard; Günther, Christian; Ochse, Michael; Schupp, O.; Tasler, Stefan

doi:10.1007/978-3-7091-6227-9_1

Cited by 74 publications

(55 citation statements)

References 1,123 publications

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“…Still, these natural products did not exhibit any optical rotation, 95 and thus might be racemic in nature, like quite a few other chiral natural biaryls. [99][100][101] To investigate the existence of possible atropo-enantiomers of 11-14 and to determine their natural ratio, a method for the enantiomeric resolution by HPLC on a chiral phase was developed, starting with parvistemin A (11) as the ''parent compound.'' The best results were achieved with a Chiralcel OD-H column (Daicel) and n-hexane/ipropanol (97.5/2.5) as the eluent at elevated temperatures (558C), providing a perfect baseline separation.…”

Section: Parvestimins-constitutionally Symmetric Bisbenzoquinonesmentioning

confidence: 99%

“…Another, stereochemically likewise highly demanding type of natural products, are the naphthylisoquinoline alkaloids, as intensely investigated in the authors' group. 111,112 These secondary metabolites constitute a rapidly growing class of structurally, biosynthetically, and pharmacologically unique naturally occurring biaryls with about 120 characterized representatives so far, all of them from plants belonging to the Ancistrocladaceae and Dioncophyllaceae, 99 thus likewise serving as a phytochemical marker for these two closely 8related tropical plant families. In contrast to most other alkaloids of this type, which are based on a configurationally more or less stable biaryl system, i.e., with a C,C axis connecting the isoquinoline and naphthalene portions, ancisheynine (16) as recently been isolated by Butler et al, 113 is the first N,C-coupled naphthylisoquinoline alkaloid.…”

Section: Isoplagiochin C-a Macrocycle Withmentioning

confidence: 99%

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The online assignment of the absolute configuration of natural products: HPLC‐CD in combination with quantum chemical CD calculations

et al. 2008

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The application of modern online methods, e.g., HPLC-MS/MS and HPLC-NMR, allows the elucidation of constitutions and relative configurations of new natural products directly from crude extracts. To additionally establish the full absolute configurations of such secondary metabolites without the necessity of first isolating the compounds, we have introduced HPLC-CD coupling (CD = circular dichroism) into natural product analysis, taking advantage of the different chiroptical properties of stereoisomers, in particular of enantiomers. In combination with quantum chemical CD calculations this method allows the stereochemical characterization of (even structurally unprecedented) chiral molecules, thus avoiding the--often risky--merely empirical assignment by comparison with the CD spectra of related compounds with known absolute stereostructures, or by other methods such as, e.g., the exciton chirality approach. This review presents the experimental requirements for the hyphenation and the theoretical background of the calculation of UV and CD spectra, which is then exemplified by some recent HPLC-CD applications to the elucidation of absolute configurations of most diverse compounds of mainly natural origin.

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Section: Parvestimins-constitutionally Symmetric Bisbenzoquinonesmentioning

confidence: 99%

Section: Isoplagiochin C-a Macrocycle Withmentioning

confidence: 99%

The online assignment of the absolute configuration of natural products: HPLC‐CD in combination with quantum chemical CD calculations

et al. 2008

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“…13.71), at the biaryl chiral axis has been determined to be (P aS) by application of exciton chirality method (Sect. 2.14) though the two interacting groups are not identical along the biphenyl axis-one is a monomer and the other is a dimer [67].…”

Section: Some Commentsmentioning

confidence: 98%

“…The monomers may be connected through oxidative coupling to form the biaryl axis. Some dimers occur as biaryl ethers; some trimers contain both ether and biaryl linkages [67]. The structures of a few dimeric coumarins and a trimeric coumarin with chiral biaryl axes are depicted in Fig.…”

Section: Some Commentsmentioning

confidence: 99%

Shikimic Acid Pathway

Talapatra

2014

Chemistry of Plant Natural Products

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“…These quinolinium salts are analogs of the N,Ccoupled naphthylisoquinolines (18,19) representing a subclass of the naphthylisoquinoline alkaloids (20)(21)(22). After the discovery of ancisheynine, the first cationic (since N,C-coupled) naphthylisoquinoline, in 2003 by Yang and coworkers (18), these secondary metabolites have aroused much stereochemical and synthetic interest (23)(24)(25) because of their promising biological activities, e.g., against Leishmania, Plasmodium, and Trypanosoma (16,26).…”

mentioning

confidence: 99%

A Novel Leishmania major Amastigote Assay in 96-Well Format for Rapid Drug Screening and Its Use for Discovery and Evaluation of a New Class of Leishmanicidal Quinolinium Salts

Bringmann

Thomale

Bischof

et al. 2013

Antimicrob Agents Chemother

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bIn most laboratories, the screening for leishmanicidal compounds is carried out with Leishmania promastigotes or axenic amastigotes. However, the best approach to identify leishmanicidal compounds is the use of amastigotes residing in macrophages. Reporter gene-based assays are relatively new tools in the search for drugs against eucaryotic protozoa, permitting the development of faster, more automated assays. In this paper, we report on the establishment of a rapid screening assay in a 96-well format. A luciferase-transgenic (Luc-tg) Leishmania major strain was generated and used to infect bone marrow-derived macrophages (BMDM). Amastigote-infected BMDM were treated with different compound concentrations. Cells were lysed with a luciferin-containing buffer, and the resulting luminescence was measured to determine the half-maximal inhibitory concentration (IC 50 ). To validate this new amastigote screening assay, a library of a new class of quinolinium salts was synthesized and tested for leishmanicidal activity. Some of the quinolinium salts showed very promising activities, with IC 50 s against intracellular amastigotes (IC 50 < 1 g/ml) and selectivity indices (SI > 20) that match the criteria of World Health Organization (WHO) for hits. Compound 21c (IC 50 ‫؍‬ 0.03 g/ml; SI ‫؍‬ 358) could become a new lead structure for the development of improved chemotherapeutic drugs against L. major. In summary, we describe the establishment of a new 96-well format assay with Luc-transgenic L. major for the rapid screening of compounds for leishmanicidal activity against intracellular amastigotes and its application to the identification of a new class of quinolinium salts with most promising leishmanicidal activity.

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Biaryls in Nature: A Multi-Facetted Class of Stereochemically, Biosynthetically, and Pharmacologically Intriguing Secondary Metabolites

Cited by 74 publications

References 1,123 publications

The online assignment of the absolute configuration of natural products: HPLC‐CD in combination with quantum chemical CD calculations

The online assignment of the absolute configuration of natural products: HPLC‐CD in combination with quantum chemical CD calculations

Shikimic Acid Pathway

A Novel Leishmania major Amastigote Assay in 96-Well Format for Rapid Drug Screening and Its Use for Discovery and Evaluation of a New Class of Leishmanicidal Quinolinium Salts

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