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The jerangolids are a class of natural products with a skipped diene substructure isolated from Sorangium cellulosum. Here, we present a new strategy for the total synthesis of these compounds based on a skipped diyne as central building block and a suitably substituted epoxy aldehyde as building block for the dihydropyran substructure. So far, we reached an advanced intermediate which is related to the pharmacophore subunit of the jerangolids as well as of the ambruticins. A key step is a Shi epoxidation with high e.r. to form the epoxy aldehyde. Both building blocks are coupled in a Carreira alkynylation, where additional mechanistic studies based on DFT calculation were realized. The alkynylation is followed by a nucleophilic 6‐endo‐tet epoxide opening to form the pyran structure and a Nicholas reduction to remove a propargylic OH group. [ABSTRACT FROM AUTHOR]

ABSTRACT Myrtucommulone-A is the active compound derived from Myrtus communis. The molecular targets of myrtucommulone-A is widely unknown, which impedes its potential therapeutic use. In this study, we demonstrated the cytotoxicity of MC-A and its potential to induce apoptosis in cancer cells. Myrtucommulone-A was also found to be antiproliferative and strongly inhibited cancer cell migration. Eighty four apoptotic pathway genes were used to assess the effect of myrtucommulone-A on cancer cells. Myrtucommulone-A mediated an increase in apoptotic genes including Fas, FasL, Gadd45a, Tnf, Tnfsf12, Trp53, and caspase 4. The increase in myrtucommulone-A dose (25 μM versus 6.25 μM) also upregulated the expression of genes, which are involved mainly in apoptosis, regulation of apoptosis, role of mitochondria in apoptotic signaling, cytokine activity, and tumor necrosis factor signaling. Our data indicate that myrtucommulone-A could be utilized as a potential therapeutic compound with its molecular targets in apoptotic pathways. [ABSTRACT FROM AUTHOR]

Besides all their conformational degrees of freedom, drug-like molecules and natural products often also undergo tautomeric interconversions. Compared to the huge efforts made in experimental investigation of tautomerism, open and free algorithmic solutions for prototropic tautomer generation are surprisingly rare. The few freely available software packages limit their output to a subset of the possible configurational space by sometimes unwanted prior assumptions and complete neglection of ring-chain tautomerism. Here, we describe an adjustable fully automatic tautomer enumeration approach, which is freely available and also incorporates the detection of ring-chain variants. The algorithm is implemented in the MolTPC framework and accessible on SourceForge. [ABSTRACT FROM AUTHOR]

Myrtucommulone A ( 1), which was isolated from myrtle and other species of the myrtaceae family, was synthesized through an enantioselective Michael addition of isobutyryl phloroglucinol ( 5) to isobutylidene syncarpic acid ( 4) that was induced by a chiral Al-Li-BINOL (1,1′-bi-2-naphthol) complex [( S, S)-ALB]. Because there is significant steric crowding in Michael acceptor 4, myrtucommulone A ( 1) was obtained with an ee value of 70 % along with meso- 1 in 77 % chemical yield. [ABSTRACT FROM AUTHOR]

Das Eisen ‐ Schwefel ‐ Protein IspH katalysiert einen Schlüsselschritt in der Biosynthese von Isoprenoiden in Bakterien und Malariaparasiten. Kristallstrukturen von IspH in Komplex mit drei Substratanaloga klären den Bindungsmodus auf und eröffnen neue Wege für die Wirkstoffentwicklung. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Resins of the genus Boswellia are currently an interesting topic for pharmaceutical research since several pharmacological activities (e.g. anti-inflammatory, anti-microbial, anti-tumour) are reported for extracts and compounds isolated from them. Unambiguous identification of these resins, by simple and convenient analytical methods, has so far not clearly been verified. Objective For differentiation and identification of three important Boswellia species ( Boswellia serrata Roxb., Boswellia papyrifera Hochst. and Boswellia carterii Birdw., respectively Boswellia sacra Flueck.), possible even for minimally equipped laboratories, a thin-layer chromatography (TLC) method was developed, allowing unambiguous identification of the three species. Methodology Crude resin samples (commercial samples and a voucher specimen) were extracted with methanol or diethyl ether and subjected to TLC analysis (normal phase). A pentane and diethyl ether (2:1) with 1% acetic acid eluent was used. Chromatograms were analysed by UV detection (254 nm) and dyeing with anisaldehyde dyeing reagent. Significant spots were isolated and structures were assigned (mass spectrometry; nuclear magnetic resonance spectroscopy). Results Incensole and incensole acetate are specific biomarkers for Boswellia papyrifera. Boswellia carterii/ Boswellia sacra reveal ß-caryophyllene oxide as a significant marker compound. Boswellia serrata shows neither incensole acetate nor ß-caryophyllene oxide spots, but can be identified by a strong serratol and a sharp 3-oxo-8,24-dien-tirucallic acid spot. Conclusion The TLC method developed allows unambiguous identification of three different olibanum samples ( Boswellia papyrifera, Boswellia serrata, Boswellia carterii/ Boswellia sacra). Evidence on the specific biosynthesis routes of these Boswellia species is reported. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]