Palladiumkatalysierte C(sp2)-H-Funktionalisierung : neue Strategien zur selektiven Synthese disubstituierter planar chiraler [2.2]Paracyclophane

Substituted [2.2]paracyclophanes are used as ligands, auxiliaries and catalysts in asymmetric synthesis due to their planar chirality. Herein, disubstituted [2.2]paracyclophanes have shown very high activity and selectivity compared to monosubstituted [2.2]paracyclophanes. However, their synthesis is still quite challenging and a regioselective functionalization of monosubstituted [2.2]paracyclophanes is restricted to a few special examples. Therefore, new strategies for the regioselective synthesis of disubstituted [2.2]paracyclophanes were investigated within this thesis. The first part describes a palladium-mediated synthesis of planar chiral carbazoles bearing a [2.2]paracyclophane backbone. These carbazoles were obtained by a palladium-catalyzed Buchwald-Hartwig amination of 4-bromo[2.2]paracyclophane and aniline or aniline derivatives followed by an intramolecular palladium-mediated cyclization under oxidative conditions. The corresponding carbazoles were formed in moderate to good yields by an ortho-selective, double C–H-functionalization of N-phenyl[2.2]paracyclophanylamines as the key step. Afterwards, the palladium-catalyzed intermolecular C–H-functionalization of various donor-substituted [2.2]paracyclophanes was investigated. A broad range of amido-, imino/oximo- and heterocyclic-substituted [2.2]paracyclophanes was prepared and their directing properties were tested in a palladium-catalyzed direct acetoxylation. Among the donor-substituted [2.2]paracyclophanes tested, both planar chiral oximethers and -acetate as well as pyridinyl- and pyrazolylsubstituted [2.2]paracyclophanes were used successfully. Ortho-acetoxylated [2.2]paracyclophanes were formed in good yields up to 87% in the presence of 1-5 mol% palladium acetate. Further functionalization of the ortho-acetoxylated [2.2]paracyclophanes yielded in promising N,O- or O,O-chelators/-ligands. In addition to the investigation of the palladium-catalyzed direct ortho-acetoxylation a mild method for the para-selective functionalization of N-acetyl-4-amino[2.2]paracyclophane was developed. The para-position was activated selectively in the presence of a hypervalent iodine(III)reagent under metal-free conditions. Using this strategy planar chiral Paracetamol derivatives were obtained in moderate to good yields

Western Star (Corner Brook, N.L.), 1908-12-02

The Western Star began publication on Newfoundland's west coast on 4 April 1900, appearing weekly with brief semiweekly periods up to 1952, when it became a daily. The current collection contains 21 April 1900 - 31 March 1926

Thiol Metabolism and Volatile Metabolome of Clostridioides difficile

Clostridioides difficile (previously Clostridium difficile) causes life-threatening gut infections. The central metabolism of the bacterium is strongly influencing toxin production and consequently the infection progress. In this context, the composition and potential origin of the volatile metabolome was investigated, showing a large number of sulfur-containing volatile metabolites. Gas chromatography/mass spectrometry (GC/MS)-based headspace analyses of growing C. difficile 630Δerm cultures identified 105 mainly sulfur-containing compounds responsible of the typical C. difficile odor. Major components were identified to be 2-methyl-1-propanol, 2-methyl-1-propanethiol, 2-methyl-1-butanethiol, 4-methyl-1-pentanethiol, and as well as their disulfides. Structurally identified were 64 sulfur containing volatiles. In order to determine their biosynthetic origin, the concentrations of the sulfur-containing amino acids methionine and cysteine were varied in the growth medium. The changes observed in the volatile metabolome profile indicated that cysteine plays an essential role in the formation of the sulfur-containing volatiles. We propose that disulfides are derived from cysteine via formation of cystathionine analogs, which lead to corresponding thiols. These thiols may then be oxidized to disulfides. Moreover, methionine may contribute to the formation of short-chain disulfides through integration of methanethiol into the disulfide biosynthesis. In summary, the causative agents of the typical C. difficile odor were identified and first hypotheses for their biosynthesis were proposed

Rhodium-Catalyzed C3-Selective Alkenylation of Substituted Thiophene-2-carboxylic Acids and Related Compounds

The regioselective C3-alkenylation of thiophene-2-carboxylic acids can be achieved effectively via rhodium/silver-catalyzed oxidative coupling with alkenes, unaccompanied by decarboxylation. A wide range of substrates including brominated thiophenecarboxylic acids and furan-2-carboxylic acids can be employed together with styrenes as well as acrylates. The present catalyst system is also applicable to ortho-alkenylation of benzoic acids

Tracking gene expression and oxidative damage of O-stressed Clostridioides difficile by a multi-omics approach.

Clostridioides difficile is the major pathogen causing diarrhea following antibiotic treatment. It is considered to be a strictly anaerobic bacterium, however, previous studies have shown a certain and strain-dependent oxygen tolerance. In this study, the model strain C. difficile 630Δerm was shifted to micro-aerobiosis and was found to stay growing to the same extent as anaerobically growing cells with only few changes in the metabolite pattern. However, an extensive change in gene expression was determined by RNA-Seq. The most striking adaptation strategies involve a change in the reductive fermentation pathways of the amino acids proline, glycine and leucine. But also a far-reaching restructuring in the carbohydrate metabolism was detected with changes in the phosphotransferase system (PTS) facilitated uptake of sugars and a repression of enzymes of glycolysis and butyrate fermentation. Furthermore, a temporary induction in the synthesis of cofactor riboflavin was detected possibly due to an increased demand for flavin mononucleotid (FMN) and flavin adenine dinucleotide (FAD) in redox reactions. However, biosynthesis of the cofactors thiamin pyrophosphate and cobalamin were repressed deducing oxidation-prone enzymes and intermediates in these pathways. Micro-aerobically shocked cells were characterized by an increased demand for cysteine and a thiol redox proteomics approach revealed a dramatic increase in the oxidative state of cysteine in more than 800 peptides after 15 min of micro-aerobic shock. This provides not only a catalogue of oxidation-prone cysteine residues in the C. difficile proteome but also puts the amino acid cysteine into a key position in the oxidative stress response. Our study suggests that tolerance of C. difficile towards

Functional diversity of isoprenoid lipids in Methylobacterium extorquens PA1

© 2021 The AuthorsHopanoids and carotenoids are two of the major isoprenoid-derived lipid classes in prokaryotes that have been proposed to have similar membrane ordering properties as sterols. Methylobacterium extorquens contains hopanoids and carotenoids in their outer membrane, making them an ideal system to investigate the role of isoprenoid lipids in surface membrane function and cellular fitness. By genetically knocking out hpnE and crtB we disrupted the production of squalene and phytoene in M. extorquens PA1, which are the presumed precursors for hopanoids and carotenoids respectively. Deletion of hpnE revealed that carotenoid biosynthesis utilizes squalene as a precursor resulting in pigmentation with a C30 backbone, rather than the previously predicted canonical C40 phytoene-derived pathway. Phylogenetic analysis suggested that M. extorquens may have acquired the C30 pathway through lateral gene transfer from Planctomycetes. Surprisingly, disruption of carotenoid synthesis did not generate any major growth or membrane biophysical phenotypes, but slightly increased sensitivity to oxidative stress. We further demonstrated that hopanoids but not carotenoids are essential for growth at higher temperatures, membrane permeability and tolerance of low divalent cation concentrations. These observations show that hopanoids and carotenoids serve diverse roles in the outer membrane of M. extorquens PA1.This work was supported by the B CUBE, TU Dresden, a German Federal Ministry of Education and Research BMBF grant (to J.S., project 03Z22EN12), and a VW Foundation “Life” grant (to J.S., project 93090)