Cross-Coupling Chemistry as a Tool for the Synthesis of Diverse Heterocyclic Systems and Natural Products

My thesis consists of six publications. The first publication is a review article with the title 'The Palladium-catalysed Ullmann Cross-coupling Reaction: A Modern Variant on a Time-honored Process'. The second publication has the title 'Palladium-Catalyzed Ullmann Cross-Coupling of beta-Iodoenones and beta-Iodoacrylates with o-Halonitroarenes or o-Iodobenzonitriles and Reductive Cyclization of the Resulting Products To Give Diverse Heterocyclic Systems'. The third publication has the title 'Reductive Cyclization of o-Nitroarylated-alpha,beta-Unsaturated Aldehydes and Ketones with TiCl3/HCl or Fe/HCl Leading to 1,2,3,9-Tetrahydro-4H-carbazol-4-ones and Related Heterocycles'. The fourth publication has the title 'Synthesis of a Highly Functionalised and Homochiral 2-Iodocyclohexenone Related to the C-Ring of the Polycyclic, Indole Alkaloids Aspidophytine and Haplophytine'. The fifth publication has the title 'Syntheses of Structurally and Stereochemically Varied Forms of C7N Aminocyclitol Derivatives from Enzymatically-derived and Homochiral cis-1,2-Dihydrocatechols' and the last publication is a review article with the title 'Chemical Syntheses of the Cochliomycins and Certain Related Resorcylic Acid Lactones'

Chemical syntheses of the cochliomycins and certain related resorcylic acid lactones

The cochliomycins (7–12) are a group of six resorcylic acid lactones that have recently been isolated from culture broths of marine fungi found in the South China Sea. These natural products have attracted attention as synthetic targets because of (in certain instances) their novel structural features and their capacities to suppress biofouling. This short review summarizes the synthesis of these and some related compounds that have been reported to date, including those developed in the authors’ laboratories.The authors thank the Australian Research Council and the Institute of Advanced Studies at the Australian National University for ongoing support. YZ is the grateful recipient of a stipend from the China Scholarship Council of the People’s Republic of China while XM thanks the Guangdong Province’s GEP for the provision of a scholarship

EvoPipes.net: Bioinformatic Tools for Ecological and Evolutionary Genomics

Recent increases in the production of genomic data are yielding new opportunities and challenges for biologists. Among the chief problems posed by next-generation sequencing are assembly and analyses of these large data sets. Here we present an online server, http://EvoPipes.net, that provides access to a wide range of tools for bioinformatic analyses of genomic data oriented for ecological and evolutionary biologists. The EvoPipes.net server includes a basic tool kit for analyses of genomic data including a next-generation sequence cleaning pipeline (SnoWhite), scaffolded assembly software (SCARF), a reciprocal best-blast hit ortholog pipeline (RBH Orthologs), a pipeline for reference protein-based translation and identification of reading frame in transcriptome and genomic DNA (TransPipe), a pipeline to identify gene families and summarize the history of gene duplications (DupPipe), and a tool for developing SSRs or microsatellites from a transcriptome or genomic coding sequence collection (findSSR). EvoPipes.net also provides links to other software developed for evolutionary and ecological genomics, including chromEvol and NU-IN, as well as a forum for discussions of issues relating to genomic analyses and interpretation of results. Overall, these applications provide a basic bioinformatic tool kit that will enable ecologists and evolutionary biologists with relatively little experience and computational resources to take advantage of the opportunities provided by next-generation sequencing in their systems

Palladium-Catalyzed Ullmann Cross-Coupling of β‑Iodoenones and β‑Iodoacrylates with o‑Halonitroarenes or o‑Iodobenzonitriles and Reductive Cyclization of the Resulting Products To Give Diverse Heterocyclic Systems

The palladium-catalyzed Ullmann cross-coupling of β-iodoenones and β-iodoacrylates such as 5 (X = I) with ohalonitroarenes and o-iodobenzonitriles including 2 affords products such as compound 7. These can be engaged in a range of reductive cyclization reactions leading to heterocyclic frameworks such as 3,4-benzomorphan derivative 43.We thank the Australian Research Council for financial support. F.K. is the grateful recipient of a scholarship provided by the Australian National University, and X.L. acknowledges the support of Circa Pty Ltd (Melbourne), while M.K. thanks the Higher Education Commission of Pakistan for funding

Phylogenetic evidence for the invasion of a commercialized European Phasmarhabditis hermaphrodita lineage into North America and New Zealand

Biological control (biocontrol) as a component of pest management strategies reduces reliance on synthetic chemicals, and seemingly offers a natural approach that minimizes environmental impact. However, introducing a new organism to new environments as a classical biocontrol agent can have broad and unanticipated biodiversity effects and conservation consequences. Nematodes are currently used in a variety of commercial biocontrol applications, including the use of Phasmarhabditis hermaphrodita as an agent targeting pest slug and snail species. This species was originally discovered in Germany, and is generally thought to have European origins. P. hermaphrodita is sold under the trade name Nemaslug®, and is available only in European markets. However, this nematode species was discovered in New Zealand and the western United States, though its specific origins remained unclear. In this study, we analyzed 45 nematode strains representing eight different Phasmarhabditis species, collected from nine countries around the world. A segment of nematode mitochondrial DNA (mtDNA) was sequenced and subjected to phylogenetic analyses. Our mtDNA phylogenies were overall consistent with previous analyses based on nuclear ribosomal RNA (rRNA) loci. The recently discovered P. hermaphrodita strains in New Zealand and the United States had mtDNA haplotypes nearly identical to that of Nemaslug®, and these were placed together in an intraspecific monophyletic clade with high support in maximum likelihood and Bayesian analyses. We also examined bacteria that co-cultured with the nematode strains isolated in Oregon, USA, by analyzing 16S rRNA sequences. Eight different bacterial genera were found to associate with these nematodes, though Moraxella osloensis, the bacteria species used in the Nemaslug® formulation, was not detected. This study provided evidence that nematodes deriving from the Nemaslug® biocontrol product have invaded countries where its use is prohibited by regulatory agencies and not commercially available

Zur Methodenentwicklung im Entwurf automobiler Strukturkonzepte in FVK-Metall-Hybridbauweise unter Crashbelastung

Hybride Materialsysteme aus FVKs und Metallen sind ein vielversprechender Ansatz, um den stetig steigenden Anforderungen an die passive Sicherheit und die energetische Effizienz im Betrieb zukünftiger Fahrzeuggenerationen durch effektive Leichtbaumaßnahmen in der Rohkarosserie gerecht zu werden. Für die erfolgreiche, technische Implementierung neuartiger Materialsysteme ist ein profundes Verständnis der Mechanismen unter Last und Versagen durch experimentelle Untersuchungen, Methoden zur gezielten Materialauswahl für eine spezielle Strukturanwendung und prognosefähige Auslegungsmethoden mithilfe numerischer Simulation nötig. Bisherige wissenschaftliche Studien beschränken sich in der Regel auf die Untersuchung Metall-intensiver Hybridsysteme und zeichnen sich, aufgrund des allgemein großen Parameterraums und ihrer meist sehr spezifischen Fragestellungen, durch eine mangelnde Vergleichbarkeit aus. Weiterhin fehlt die integrative Herangehensweise an die drei nötigen Disziplinen, um die Vorteile einer konsistenten Datenbasis und Synergien nutzbar zu machen. Die, in dieser Arbeit vorgestellte, multidisziplinäre Gesamtmethodik verfolgt erstmalig diesen integrativen Ansatz und bearbeitet gleichzeitig wissenschaftliche Fragestellungen in den Einzeldisziplinen. Die umfangreichen experimentellen Untersuchungen erschließen dabei neue Parameterräume FVK-intensiver Hybridsysteme unter quasistatischer und dynamischer Last mit einem konsistenten Materialspektrum über mehrere Ebenen der Strukturkomplexität. Diese Datenbasis nutzt eine neue, objektive Methode zur Eignungsbewertung und Auswahl hybrider Materialsysteme für eine spezielle Strukturanwendung auf Basis ihres überlagerten Beanspruchungsprofils aus den relevanten Crash-Lastfällen. Weiterhin dienen diese Daten als Grundlage zur Analyse und Bewertung vereinfachter, effizienter Modellierungsmethoden für die Simulation des Crashverhaltens hybrider Strukturen in der Konzeptphase mittels Komplexitäts- und Sensitivitätsstudien. Ein neues Phänomen des nichtlokalen Schädigungsverhaltens im Klebstoff-Interface von FVK-Metall-Hybridsystemen unter Zugbelastung wird beschrieben, experimentell untersucht und in ein prognosefähiges, analytisches Modell überführt. Die Ergebnisse der numerischen Studien indizieren, dass die Erweiterung eines stark vereinfachten, starren Interface-Modells um das entwickelte Modell der nicht-lokalen Schädigung einen zielführenden Kompromiss zwischen Modellgenauigkeit und Ressourceneffizienz darstellt. Die Umsetzung der multidisziplinären Gesamtmethodik auf ein reales Fahrzeugsubsystem mit experimentellen alidierungsversuchen belegt ihre generell Anwendbarkeit, offenbart jedoch gleichzeitig vielseitige Potenziale zur Weiterentwicklung und Achtungspunkte bei der Anwendung

Synthesis of a Highly Functionalised and Homochiral 2-Iodocyclohexenone Related to the C-Ring of the Polycyclic, Indole Alkaloids Aspidophytine and Haplophytine

The enzymatically-derived and enantiomerically pure (1S,2S)-3-bromocyclohexa-3,5-diene-1,2-diol (7) has been elaborated over 10 steps into cyclohexenone 8. The latter compound embodies the enantiomeric form of the C-ring associated with the hexacyclic framework of the alkaloid aspidophytine (2). As such, this work sets the stage for effecting the conversion of the enantiomeric metabolite ent-7 into compound ent-8, and thence, through previously established protocols, including a palladium-catalysed Ullmann cross-coupling reaction, into the title alkaloids

Stress and resources in women attending an inpatient prevention/rehabilitation measure for parents: Secondary analysis of quality assurance data

Questionnaire data from two projects on the development of quality assurance instruments for an inpatient rehabilitation/prevention program for parents were used for a secondary analysis. In this analysis, the associations of gains in a psychosocial resource (parenting self-efficacy) and two types of stressors experienced by mothers at the start of treatment (parenting hassles, depressive symptoms) with general life satisfaction and satisfaction with health at the end of treatment were explored. Structural equation modeling was applied to data from N = 1724 female patients. Potential resource-stressor interactions were tested using the Latent Moderated Structural Equations approach. Results showed that parenting hassles were negatively associated with general life satisfaction and satisfaction with health while self-efficacy gains were weakly positively correlated with both variables. No interaction of parenting hassles and self-efficacy gains was found. Depressive symptoms were negatively associated with both satisfaction measures. In these models, self-efficacy gains were not substantially correlated with life satisfaction, but showed a small association with satisfaction with health. There was no significant interaction of depressive symptoms and self-efficacy gains. The findings imply that interventions for distressed mothers—as exemplarily illustrated by this inpatient setting—should focus on identifying and reducing initial stressors as these may continue to impair mothers’ subjective health despite gains in parenting-related resources

The Palladium-Catalyzed Ullmann Cross-Coupling Reaction: A Modern Variant on a Time-Honored Process

ConspectusCross-coupling reactions, especially those that are catalyzed by palladium, have revolutionized the way in which carbon-carbon bonds can be formed. The most commonly deployed variants of such processes are the Suzuki-Miyaura, Mizoroki-Heck, Stille, and Negishi cross-coupling reactions, and these normally involve the linking of an organohalide or pseudohalide (such as a triflate or nonaflate) with an organo-metallic or -metalloid such as an organo-boron, -magnesium, -tin, or -zinc species. Since the latter type of coupling partner is often prepared from the corresponding halide, methods that allow for the direct cross-coupling of two distinct halogen-containing compounds would provide valuable and more atom-economical capacities for the formation of carbon-carbon bonds. While the venerable Ullmann reaction can in principle achieve this, it has a number of drawbacks, the most significant of which is that homocoupling of the reaction partners is a competitive, if not the dominant, process. Furthermore, such reactions normally occur only under forcing conditions (viz., often at temperatures in excess of 250 °C). As such, the Ullmann reaction has seen only limited application in this regard, especially as a mid- to late-stage feature of complex natural product synthesis. This Account details the development of the palladium-catalyzed Ullmann cross-coupling reaction as a useful method for the assembly of a range of heterocyclic systems relevant to medicinal and/or natural products chemistry. These couplings normally proceed under relatively mild conditions (<100 °C) over short periods of time and, usually, to the exclusion of (unwanted) homocoupling events. The keys to success are the appropriate choice of coupling partners, the form of the copper metal employed, and the choice of reaction solvent.At the present time, the cross-coupling partners capable of engaging in the title reaction are confined to halogenated and otherwise electron-deficient arenes and, as complementary reactants, α- or β-halogenated, α,β-unsaturated aldehydes, ketones, esters, lactones, lactams, and cycloimides. Nitro-substituted (and halogenated) arenes, in particular, serve as effective participants in these reactions, and the products of their coupling with the above-mentioned carbonyl-containing systems can be manipulated in a number of different ways. Depending on the positional relationship between the nitro and carbonyl groups in the cross-coupling product, the reduction of the former group, which can be achieved under a range of different conditions, provides, through intramolecular nucleophilic addition reactions, including Schiff base condensations, access to a diverse range of heterocyclic systems. These include indoles, quinolines, quinolones, isoquinolines, carbazoles, and carbolines. Tandem variants of such cyclization processes, in which Raney cobalt is used as a catalyst for the chemoselective reduction (by dihydrogen) of nitro and nitrile groups (but not olefins), allow for the assembly of a range of structurally challenging natural products, including marinoquinoline A, (±)-1-acetylaspidoalbidine, and (±)-gilbertine.The authors thank the Australian Research Council and the Institute of Advanced Studies at the Australian National University for ongoing support

Experimental investigation and evaluation of numerical modeling approaches for hybrid-FRP-steel sections under impact loading for the application in automotive crash-structures

A large body of work has studied the energy absorption of metallic and composite tubes undergoing crushing. Similarly, reinforcements of metallic structures with composites have also been studied. By contrast, composite tubes with metallic reinforcements (composite-intensive) have not been investigated, although they may offer benefits in terms of robustness or cost over both composite as well as metallic tubes. Here, composite materials with metallic reinforcements were tested under dynamic axial loading in order to study the effects of major design parameters on the energy absorption and load uniformity behavior. Significant benefits could be identified, particularly when considering cost aspects. Two numerical approaches for modeling the adhesive interface between the two discrete material phases were evaluated in terms of accuracy and efficiency in crash simulations. The simplified modeling technique comprising two layers of shell elements rigidly tied at the interface proved to be generally applicable to the evaluation of structural concepts in an early vehicle development stage