Studien zur Totalsynthese der Naturstoffe (-)-Englerin A und Crotogoudin

In the first part of the thesis four different approaches to the core structure of the novel guaiane sesquiterpene englerin A are described. The first approach features a Rh(II)-catalyzed generation of a cyclic carbonyl ylide from a diazoketone precursor which was trapped with allyl propiolate. The 1,3-dipolar cycloaddition led to the stereoselective formation of an oxygen-bridged polycyclic structure, however with opposite stereochemistry of the ether bridge compared to natural englerin. In further studies the core structure of the sesquiterpene was prepared by an oxy-Cope rearrangement/transannular epoxide opening sequence. Utilizing this strategy an analogue of the natural product without a glycolate at C-9 (9-deoxy-englerin) was synthesized. Studies on the cytotoxic activity of this analog proved the importance of the hydroxyl group and glycolic acid at C-9. The second part describes studies on the total synthesis of another terpene – crotogoudin. The key bicyclo[2.2.2]octane subunit was constructed by an early stage domino Michael reaction. Subsequent Stork reductive alkylation resulted in an opposite stereochemistry at C-10 in respect to the one in natural crotogoudin. Attempts to perform a late stage double Michael reaction were not successful, however the total synthesis of another diterpene – moluccanic acid, was achieved from the common intermediate.Im ersten Teil der Dissertation wurden vier verschiedene Zugänge zur Kernstruktur des neuen Guajan-Sesquiterpens Englerin A entwickelt. Die erste Methode beinhaltet eine Rh(II)- katalysierte Bildung eines cyclischen Carbonylylides aus einer Diazoketon-Vorstufe, welche mittels Allylpropiolat abgefangen wurde. Die 1,3-dipolare Cycloaddition führte zur stereoselektiven Bildung einer sauerstoffverbrückten polycyclischen Struktur, jedoch wies die Etherbrücke im Vergleich zu Englerin A die entgegengesetzte Stereochemie auf. In weiteren Studien konnte die Kernstruktur des Sesquiterpens über eine Oxy-Cope Umlagerung und anschließende transannulare Epoxidöffnung erhalten werden. Mittels dieser Synthesestrategie konnte ein Analogon des Naturstoffes, ohne Glykolat an C-9 synthetisiert werden. Studien zur cytotoxischen Aktivität des Analogons bewiesen die bedeutende Rolle der Hydroxygruppe und der Glykolsäure an C-9. Der zweite Teil der Dissertation befasst sich mit Studien zur Totalsynthese eines weiteren Terpens- Crotogoudin. Die Schlüsselverbindung ein Bicyclo[2.2.2]octan wurde über eine Domino Michael Reaktion in einem frühen Stadium der Synthese aufgebaut. Die anschließende Stork Alkylierung führte zur entgegengesetzten Stereochemie an C-10, verglichen mit dem Naturstoff Crotogoudin. Der Versuch einer doppelten Michaeladdition in einem späten Stadium der Synthese scheiterte, jedoch war die Totalsynthese eines anderen Diterpens erfolgreich - Moluccansäure, diese konnte aus dem gemeinsamen Intermediat synthetisiert werden

Natural Killer Cell Signal Integration Balances Synapse Symmetry and Migration

Imaging immune surveillance by natural killer (NK) cells has revealed that integration of activating and inhibitory signals determines whether or not NK cells stop to kill the target cell or retain a migratory configuration

Synthesis of α‑Nitro Carbonyls via Nitrations in Flow

Reported is a safe, rapid method for the synthesis of α-nitro esters via the trapping of nitronium ions. The two-stage nitration and subsequent deacetylation of readily available 1,3-dicarbonyl compounds was achieved using a biphasic semicontinuous approach. α-Nitro esters and amides were obtained in good overall yields (53–84%). Some of the α-nitro-1,3-dicarbonyl intermediates exhibit enhanced reactivity and undergo an acid-catalyzed Nef-type reaction to α-oxo-carbonyls

Rarely naturalized, but widespread and even invasive: the paradox of a popular pet terrapin expansion in Eurasia

The North American terrapin, the red-eared slider, has globally recognized invasive status. We built a new extensive database using our own original and literature data on the ecology of this reptile, representing information on 1477 water bodies throughout Eurasia over the last 50 years. The analysis reveals regions of earliest introductions and long-term spatio-temporal dynamics of the expansion covering now 68 Eurasian countries, including eight countries reported here for the first time. We established also long-term trends in terms of numbers of terrapins per aquatic site, habitat occupation, and reproduction success. Our investigation has revealed differences in the ecology of the red-eared slider in different parts of Eurasia. The most prominent expression of diverse signs of invasion success (higher portion of inhabited natural water bodies, higher number of individuals per water body, successful overwintering, occurrence of juvenile individuals, successful reproduction, and establishment of populations) are typical for Europe, West Asia and East Asia and tend to be restricted to coastal regions and islands. Reproduction records coincide well with the predicted potential range based on climatic requirements but records of successful wintering have a wider distribution. This invader provides an excellent and possibly unique (among animals) example of wide alien distribution, without the establishment of reproducing populations, but through the recruitment of new individuals to rising pseudopopulations due to additional releases. Therefore, alongside the potential reproduction range, a cost-effective strategy for population control must take in account the geographical area of successful wintering. Graphical abstrac

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes