Precursor‐Directed Syntheses and Biological Evaluation of New Elansolid Derivatives

Steinmetz, Heinrich; Zander, Wiebke; Shushni, Muftah A. M.; Jansen, Rolf; Gerth, Klaus; Dehn, Richard; Dräger, Gerald; Kirschning, Andreas; Müller, Rolf

doi:10.1002/cbic.201200228

Cited by 26 publications

(43 citation statements)

References 10 publications

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“…This excellent facial selectivity has been demonstrated, e.g., for anilines as nucleophiles before. It is due to the preferred conformation around the bond at C24–C25 which leads to the efficient shielding of the si -face by the two germinal methyl groups at C22 [4–5]. The NMR data determined for both synthetic products were identical with those of authentic samples of elansolid B1 ( 2 ) and elansolid B2 ( 3 ) (copies of spectra, see Supporting Information File 1).…”

Section: Resultsmentioning

confidence: 79%

Total synthesis of elansolids B1 and B2

Wang¹,

Kirschning²

2017

Beilstein J. Org. Chem.

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The elansolids A1–A3, B1, and B2 are secondary metabolites formed by the gliding bacterium Chitinophaga sancti. They show antibacterial activity against Gram-positive bacteria. A second generation total synthesis of the antibiotic elansolid B1 (2) and the first synthesis of elansolid B2 (3) are reported. In contrast to previous work, the (Z,E,Z)-triene at C10–C15 was assembled by using an optimized C–C cross-coupling sequence with a Suzuki cross-coupling reaction as key step.

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Section: Resultsmentioning

confidence: 79%

Total synthesis of elansolids B1 and B2

Wang¹,

Kirschning²

2017

Beilstein J. Org. Chem.

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“…23a Another recent example is the generation of derivatives of the antibiotic elansolid via a conjugate addition of arylamines to a p -quinone methide generated under mildly basic conditions. 24 Each of these examples; the ammosamides, jadomycin and elansolid take advantage of a different reactive functional group and a different chemical transformation for analog generation, but represent a powerful approach to obtain analogs of natural products with suitable reactive intermediates.…”

Section: Resultsmentioning

confidence: 99%

Precursor-directed generation of amidine containing ammosamide analogs: ammosamides E–P

et al. 2013

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Ammosamides E-F (1-2), are amidine analogs of the ammosamide family of alkaloids isolated from a marine-derived Streptomyces variabilis. Further studies with S. variabilis revealed a variety of aryl and alkyl amines added into the fermentation media could be efficiently incorporated into the ammosamide framework to generate a library of precursor-directed amidine analogs, ammosamides G-P (9 – 18). We demonstrate that the amines are introduced via non-enzymatic addition to the iminium ion of ammosamide C. Biological evaluation of the amidine analogs against quinone reductase 2 (QR2) showed low nM potency for a number of analogs. When tested for in vivo activity against a panel of non-small cell lung cancer (NSCLC) cell-lines there was a clear increase in potency by incorporation of lipophilic alkylamines, with the most potent compounds having sub μM IC50 values (0.4 to 0.8 μM).

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“…Many substances are synthesized from the beginning of growth, or shortly after (Reinchenbach 2001). The new antibiotic scaffold elansolid exhibiting potent anti-MRSA activity (Steinmetz et al 2011(Steinmetz et al , 2012 was found in Chitinophaga sanctii, and the novel genus Aetherobacter was identified as a producer of a novel scaffold, the aetheramides, showing activity against HIV (Plaza et al 2012). Cystobacter ferrugineus was found to produce roimatacenes representing a novel class of antibiotics (Zander et al 2011), hyalidione was identified from Hyalangium minutum, and icumazoles (Barbier et al 2012) were described as a new class of antifungals from Sorangium cellulosum.…”

Section: Production Of Secondary Metabolitesmentioning

confidence: 99%

Current trends in myxobacteria research

et al. 2015

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Myxobacteria are fascinating Gram-negative bacteria whose life cycle includes the formation of multicellular fruiting bodies that contain about 100,000 cells differentiated as asexual spores for their long-term survival. They move by gliding on surfaces, an activity that helps them carry out their primitive kind of multicellular development. Myxobacteria have multiple traits that are clearly social in nature; they move and feed socially. These processes require specific intercellular signals, thereby exhibiting a sophisticated level of the interorganismal communication. Myxobacteria are predators. Predation is social not only with respect to searching for prey (motility) but also in the killing of prey. Swarming groups of cells secrete antibiotics and bacteriolytic compounds that kill and lyse their prey, and food is thereby released. Since the last three decades, myxobacteria are known as valuable producers of secondary metabolites exhibiting various biological activities. Myxobacterial metabolites exhibit many unique structural features as well as rare or novel modes of action, making them attractive lead structures for drug development. Both genome sequencing and metabolic profiling of myxobacterial strains suggest that the diversity of myxobacterial secondary metabolism is far greater than previously appreciated. The present review discusses the structure, cytology, physiology, and ecology of myxobacteria, as well as their secondary metabolite production and social interactions.

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Precursor‐Directed Syntheses and Biological Evaluation of New Elansolid Derivatives

Cited by 26 publications

References 10 publications

Total synthesis of elansolids B1 and B2

Total synthesis of elansolids B1 and B2

Precursor-directed generation of amidine containing ammosamide analogs: ammosamides E–P

Current trends in myxobacteria research

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