TY - JOUR A1 - Bringmann, Gerhard A1 - Ortmann, Thomas A1 - Zagst, Rainer A1 - Schoener, Bernd A1 - Assi, Laurent Ake A1 - Burschka, Christian T1 - +/- Dioncophyllacine A, a naphthylisoquinoline alkaloid with a 4-methoxy substituent from the leaves of Triphyophyllum peltatum N2 - The isolation and structure elucidation of rac-dioncophyllacine A from the leaves of Triphyophyllun peltatum, is described. Unlike all other naphthylisoquinoline alkaloids, this fully dehydrogenated representative has an additional methoxy group at C-4, the position of which is deduced from NOE results. Dioncophyllacine A has a 7,1' site of the biaryl axis, as in dioncophylline A. Its constitution is confirmed by an X-ray structure analysis, which shows that the crystalline form of this new alkaloid is racemic. KW - Dioncophyllaceae KW - Triphyophyllum peltaturn KW - Dioncophyllaceae leaves KW - (± )-dioncophyllacine A KW - naphthylisoquinoline alkaloids KW - structure elucidation Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31873 ER - TY - THES A1 - Chaidir, T1 - Insektizide Rocaglamid-Derivate und Verwandte Verbindungen aus Aglaia-Arten (Meliaceae) T1 - Insecticidal rocaglamide derivatives and related compounds from Aglaia species (Meliaceae) N2 - Auf der Suche nach neuen biologisch aktiven Naturstoffe aus der Gattung Aglaia(Meliaceae) wurde die insektizide Wirkung von Methanol-Extrakten verschiedener Aglaia-Arten gegenüber frisch geschlüpften Raupen des Schadinsektes Spodoptera littoralis (Noctuidae) untersucht. Die getesteten Proben stammen aus Vietnam und Südchina. Aus den in diesem Bioscreening aufgefallenen Extrakten wurden mit Hilfe von durch Biotests begleiteter Fraktionierung sowie parallel durchgeführten chemisch-physikalischen Analysen insgesamt 29 Naturstoffe isoliert und charakterisiert. Darunter befinden sich sechs bisher nicht beschriebene Benzofurane (Rocaglamide), zwei Benzopyrane (je ein Aglain und ein Aglaforbesin), zwei Benzoxepine (Forbagline) sowie ein Zimtsäure-Putrescin-Bisamid. Die Strukturaufklärung erfolgte vor allem durch NMR-Spektroskopie (darunter 2D-Experimente wie H-H-COSY, HMQC, HMBC und ROESY) sowie durch Massenspektrometrie. Die Untersuchungen zur Struktur-Wirkungs-Beziehung ergaben für die Rocaglamide V, Z und AA eine starke insektizide Aktivität gegenüber Raupen von S. littoralis mit LC50- und EC50-Werten von 2.0 bis 6.6 ppm bzw. 0.1 bis 1.0 ppm, während die Rocaglamide X und Y überraschenderweise keine Aktivität zeigten. Letztere stellen bisher die ersten Beispiele für biologisch inaktive Rocaglamid-Derivate überhaupt dar. Dieser Befund weist darauf hin, daß für die insektizide Aktivität dieser Verbindungs-Klasse der Hydroxyl-Substituent am C-8b neben dem Benzofuran-Grundkörper eine entscheidende Rolle spielt, da eine Alkoxylierung an C-8b zum vollständigen Verlust der Aktivität führt. In einem Screening mit drei verschiedenen basalen Medien, die mit unterschiedlichen Phytohormonen und organischen Zusätzen versetzt worden waren, erwies sich das RW-(Risser und White) Medium mit 1 mg/l 2.4-D, 0.2 mg/l BAP, 0.1 g/l Ascorbinsäure und 0.5 g/l Caseinhydrolysat als geeignetstes Kulturmedium zur Kalusbildung bei Aglaia-Arten. Die Vorversuche zeigten darüber hinaus deutlich, daß Kalluskulturen von Aglaia elliptica in der Lage sind, relevante Inhaltsstoffe wie das Zimtsäure-Pyrrolidin-Bisamid- Derivat zu bilden. N2 - In search for novel naturally bioactive compounds, a screening program was performed on ten methanol extracts from different organs of six Aglaia spp, namely, odorata, tsangii, polystachia, taiwanensis, duperreana and dasyclada, collected in Vietnam and China, using a well established insecticide-bioassay system with the polyphagous pest insect Spodoptera littoralis (Noctuidae). Bioassay-guided fractionation of those extracts using the same bioassay system, led to the isolation of twenty-nine natural compounds, eleven of which are new natural products. Six new rocaglamide derivatives along with another twelve congeners were isolated and identified. Three cinammoyl bisamide derivatives, possessing either a 2-aminopyrrolidine ring or a putrescine moeity, were obtained together with four rocaglamide-related compounds (aglain-, aglaforbesin- and forbaglin type compounds) which also possess putrescine. In addition, A. dasyclada also yielded two interesting flavonoid derivatives, flavanocoumarine and a phenylpropanoid derivative of catechin, together with catechin and scopoletine (coumarin). The structures were established on the basis of 1H, 13C and 2D (H-H-COSY, HMQC, HMBC, ROESY) NMR spectroscopic methods and mass spectrometry. The insecticidal activities of the new rocaglamide derivatives against the larvae of S. littoralis in a chronic feeding assay were calculated as LC50 and EC50-values and exhibited values ranging from 2.0 - 6.6 ppm and 0.1 - 1.0 ppm, respectively. An interesting finding however showed that two rocaglamide derivatives, both with ethyloxy-substituent at C-8b of the furan ring instead of the usual hydroxy group, were devoid of insecticidal activity. In the course of the preliminary study to establish a callus culture of Aglaia sp., Risser and White medium supplemented with 1.0 mg/l 2,4-D, 0.2 mg/l BAP, 0.5 g/l casein hydrolysate and 0.1 g/l ascorbic acid was found as the best medium for induction of callus. In this study through LC-MS experiment, the present of odorinol was also observed in the callus of A. elliptica. KW - Aglaia KW - Pflanzeninhaltsstoff KW - Pflanzliches Insektizid KW - Agalia duperreana KW - Aglaia dasyclada KW - Meliaceae KW - Rocaglamid KW - Isolierung KW - Strukturauklärung KW - NMR KW - spodoptera littoralis KW - Aglaia duperreana KW - Aglaia dasyclada KW - Meliaceae KW - rocaglamide KW - isolation KW - structure elucidation KW - NMR KW - spodoptera littoralis Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-647 ER - TY - JOUR A1 - Hecht, Markus A1 - Leowanawat, Pawaret A1 - Gerlach, Tabea A1 - Stepanenko, Vladimir A1 - Stolte, Matthias A1 - Lehmann, Matthias A1 - Würthner, Frank T1 - Self‐Sorting Supramolecular Polymerization: Helical and Lamellar Aggregates of Tetra‐Bay‐Acyloxy Perylene Bisimide JF - Angewandte Chemie International Edition N2 - A new perylene bisimide (PBI), with a fluorescence quantum yield up to unity, self‐assembles into two polymorphic supramolecular polymers. This PBI bears four solubilizing acyloxy substituents at the bay positions and is unsubstituted at the imide position, thereby allowing hydrogen‐bond‐directed self‐assembly in nonpolar solvents. The formation of the polymorphs is controlled by the cooling rate of hot monomer solutions. They show distinctive absorption profiles and morphologies and can be isolated in different polymorphic liquid‐crystalline states. The interchromophoric arrangement causing the spectral features was elucidated, revealing the formation of columnar and lamellar phases, which are formed by either homo‐ or heterochiral self‐assembly, respectively, of the atropoenantiomeric PBIs. Kinetic studies reveal a narcissistic self‐sorting process upon fast cooling, and that the transformation into the heterochiral (racemic) sheetlike self‐assemblies proceeds by dissociation via the monomeric state. KW - liquid crystals KW - noncovalent interactions KW - self-assembly KW - structure elucidation KW - supramolecular chemistry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224586 VL - 59 IS - 39 SP - 17084 EP - 17090 ER - TY - JOUR A1 - Hermann, Alexander A1 - Fantuzzi, Felipe A1 - Arrowsmith, Merle A1 - Zorn, Theresa A1 - Krummenacher, Ivo A1 - Ritschel, Benedikt A1 - Radacki, Krzysztof A1 - Engels, Bernd A1 - Braunschweig, Holger T1 - Oxidation, Coordination, and Nickel-Mediated Deconstruction of a Highly Electron-Rich Diboron Analogue of 1,3,5-Hexatriene JF - Angewandte Chemie, International Edition N2 - The reductive coupling of an N-heterocyclic carbene (NHC) stabilized (dibromo)vinylborane yields a 1,2-divinyl- diborene, which, although isoelectronic to a 1,3,5-triene, displays no extended p conjugation because of twisting of the C\(_2\)B\(_2\)C\(_2\) chain. While this divinyldiborene coordinates to copper(I) and platinum(0) in an η\(^2\)-B\(_2\) and η\(^4\)-C\(_2\)B\(_2\) fashion, respectively, it undergoes a complex rearrangement to an η\(^4\)-1,3-diborete upon complexation with nickel(0). KW - boron KW - diborenes KW - carbenes KW - conjugation KW - density-functional calculations KW - rearrangements KW - structure elucidation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240652 VL - 59 IS - 36 ER - TY - JOUR A1 - Heß, Merlin A1 - Krummenacher, Ivo A1 - Dellermann, Theresa A1 - Braunschweig, Holger T1 - Rhodium-Mediated Stoichiometric Synthesis of Mono-, Bi-, and Bis-1,2-Azaborinines: 1-Rhoda-3,2-azaboroles as Reactive Precursors JF - Chemistry—A European Journal N2 - A series of highly substituted 1,2-azaborinines, including a phenylene-bridged bis-1,2-azaborinine, was synthesized from the reaction of 1,2-azaborete rhodium complexes with variously substituted alkynes. 1-Rhoda-3,2-azaborole complexes, which are accessible by phosphine addition to the corresponding 1,2-azaborete complexes, were also found to be suitable precursors for the synthesis of 1,2-azaborinines and readily reacted with alkynyl-substituted 1,2-azaborinines to generate new regioisomers of bi-1,2-azaborinines, which feature directly connected aromatic rings. Their molecular structures, which can be viewed as boron-nitrogen isosteres of biphenyls, show nearly perpendicular 1,2-azaborinine rings. The new method using rhodacycles instead of 1,2-azaborete complexes as precursors is shown to be more effective, allowing the synthesis of a wider range of 1,2-azaborinines. KW - structure elucidation KW - azaborinines KW - nitrogen heterocycles KW - cyclization KW - metallacycles Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256830 VL - 27 IS - 37 ER - TY - JOUR A1 - Horrer, Günther A1 - Krahfuß, Mirjam J. A1 - Lubitz, Katharina A1 - Krummenacher, Ivo A1 - Braunschweig, Holger A1 - Radius, Udo T1 - N-Heterocyclic Carbene and Cyclic (Alkyl)(amino)carbene Complexes of Titanium(IV) and Titanium(III) JF - European Journal of Inorganic Chemistry N2 - The reaction of one and two equivalents of the N ‐heterocyclic carbene IMes [IMes = 1,3‐bis(2,4,6‐trimethyl‐phenyl)imidazolin‐2‐ylidene] or the cyclic (alkyl)(amino)carbene cAAC\(^{Me}\) [cAAC\(^{Me}\) = 1‐(2,6‐diisopropyl‐phenyl)‐3,3,5,5‐tetra‐methylpyrrolidin‐2‐ylidene] with [TiCl\(_{4}\)] in n ‐hexane results in the formation of mono‐ and bis‐carbene complexes [TiCl\(_{4}\)(IMes)] 1 , [TiCl\(_{4}\)(IMes)2] 2 , [TiCl\(_{4}\)(cAAC\(^{Me}\))] 3 , and [TiCl\(_{4}\)(cAAC\(^{Me}\))\(_{2}\)] 4 , respectively. For comparison, the titanium(IV) NHC complex [TiCl\(_{4}\)(Ii Pr\(^{Me}\))] 5 (Ii Pr\(^{Me}\) = 1,3‐diisopropyl‐4,5‐dimethyl‐imidazolin‐2‐ylidene) has been synthesized and structurally characterized. The reaction of [TiCl\(_{4}\)(IMes)] 1 with PMe\(_{3}\) affords the mixed substituted complex [TiCl\(_{4}\)(IMes)(PMe\(_{3}\))] 6 . The reactions of [TiCl\(_{3}\)(THF)\(_{3}\)] with two equivalents of the carbenes IMes and cAAC\(^{Me}\) in n ‐hexane lead to the clean formation of the titanium(III) complexes [TiCl\(_{3}\)(IMes)\(_{2}\)] 7 and [TiCl\(_{3}\)(cAAC\(^{Me}\))\(_{2}\)] 8 . Compounds 1 –8 have been completely characterized by elemental analysis, IR and multinuclear NMR spectroscopy and for 2 –5 , 7 and 8 by X‐ray diffraction. Magnetometry in solution, EPR and UV/Vis spectroscopy and DFT calculations performed on 7 and 8 are indicative of a predominantly metal‐centered d\(^{1}\)‐radical in both cases. KW - N-heterocyclic carbenes KW - carbene ligands KW - Titanium KW - structure elucidation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208725 VL - 2020 IS - 3 ER - TY - JOUR A1 - Ivanova, Svetlana A1 - Köster, Eva A1 - Holstein, Julian J. A1 - Keller, Niklas A1 - Clever, Guido H. A1 - Bein, Thomas A1 - Beuerle, Florian T1 - Isoreticular crystallization of highly porous cubic covalent organic cage compounds JF - Angewandte Chemie International Edition N2 - Modular frameworks featuring well-defined pore structures in microscale domains establish tailor-made porous materials. For open molecular solids however, maintaining long-range order after desolvation is inherently challenging, since packing is usually governed by only a few supramolecular interactions. Here we report on two series of nanocubes obtained by co-condensation of two different hexahydroxy tribenzotriquinacenes (TBTQs) and benzene-1,4-diboronic acids (BDBAs) with varying linear alkyl chains in 2,5-position. n-Butyl groups at the apical position of the TBTQ vertices yielded soluble model compounds, which were analyzed by mass spectrometry and NMR spectroscopy. In contrast, methyl-substituted cages spontaneously crystallized as isostructural and highly porous solids with BET surface areas and pore volumes of up to 3426 m\(^2\) g\(^{-1}\) and 1.84 cm\(^3\) g\(^{-1}\). Single crystal X-ray diffraction and sorption measurements revealed an intricate cubic arrangement of alternating micro- and mesopores in the range of 0.97–2.2 nm that are fine-tuned by the alkyl substituents at the BDBA linker. KW - organic chemistry KW - structure elucidation KW - boronateesters KW - cage compounds KW - dynamic covalent chemistry KW - porousmaterials Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256462 VL - 60 IS - 32 ER - TY - JOUR A1 - Kraft, Andreas A1 - Stangl, Johannes A1 - Krause, Ana-Maria A1 - Müller-Buschbaum, Klaus A1 - Beuerle, Florian T1 - Supramolecular frameworks based on [60]fullerene hexakisadducts JF - Beilstein Journal of Organic Chemistry N2 - [60]Fullerene hexakisadducts possessing 12 carboxylic acid side chains form crystalline hydrogen-bonding frameworks in the solid state. Depending on the length of the linker between the reactive sites and the malonate units, the distance of the [60]fullerene nodes and thereby the spacing of the frameworks can be controlled and for the most elongated derivative, continuous channels are obtained within the structure. Stability, structural integrity and porosity of the material were investigated by powder X-ray diffraction, thermogravimetry and sorption measurements. KW - chemistry KW - fullerenes KW - hexakisadducts KW - hydrogen bonding KW - porous materials KW - structure elucidation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171996 VL - 13 ER - TY - JOUR A1 - Liu, Xiaocui A1 - Ming, Wenbo A1 - Luo, Xiaoling A1 - Friedrich, Alexandra A1 - Maier, Jan A1 - Radius, Udo A1 - Santos, Webster L. A1 - Marder, Todd B. T1 - Regio‐ and Stereoselective Synthesis of 1,1‐Diborylalkenes via Brønsted Base‐Catalyzed Mixed Diboration of Alkynyl Esters and Amides with BpinBdan JF - European Journal of Organic Chemistry N2 - The NaOtBu‐catalyzed mixed 1,1‐diboration of terminal alkynes using the unsymmetrical diboron reagent BpinBdan (pin = pinacolato; dan = 1,8‐diaminonaphthalene) proceeds in a regio‐ and stereoselective fashion affording moderate to high yields of 1,1‐diborylalkenes bearing orthogonal boron protecting groups. It is applicable to gram‐scale synthesis without loss of yield or selectivity. The mixed 1,1‐diborylalkene products can be utilized in Suzuki–Miyaura cross‐coupling reactions which take place selectivly at the C–B site. DFT calculations suggest the NaOtBu‐catalyzed mixed 1,1‐diboration of alkynes occurs through deprotonation of the terminal alkyne, stepwise addition of BpinBdan to the terminal carbon followed by protonation with tBuOH. Experimentally observed selective formation of (Z)‐diborylalkenes is supported by our theoretical studies. KW - boronate esters KW - borylation KW - cross‐coupling KW - synthesis design KW - structure elucidation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214728 VL - 2020 IS - 13 SP - 1941 EP - 1946 ER - TY - JOUR A1 - Matler, Alexander A1 - Arrowsmith, Merle A1 - Schorr, Fabian A1 - Hermann, Alexander A1 - Hofmann, Alexander A1 - Lenczyk, Carsten A1 - Braunschweig, Holger T1 - Reactivity of Terminal Iron Borylenes and Bis(borylenes) with Carbodiimides: Cycloaddition, Metathesis, Insertion and C−H Activation Pathways JF - European Journal of Inorganic Chemistry N2 - The reactions of carbodiimides with the iron arylborylene complex [Fe=BDur(CO)\(_{3}\)(PMe\(_{3}\))] (Dur=2,3,5,6-Me\(_{4}\)C\(_{6}\)H) and the iron bis(borylene) complex [Fe{=BDur}{=BN(SiMe\(_{3}\))\(_{2}\)}(CO)\(_{3}\)] yield a wide variety of temperature-dependent products, including known FeBNC and novel FeBNB metallacycles, complexes of N-heterocyclic boracarbene and spiro-boracarbene ligands and a unique 1,3,2,4-diazadiborolyl pianostool complex, characterized by NMR spectroscopy and X-ray crystallography. The product distributions can be rationalized by considering sequences of cycloaddition, metathesis, insertion, and C−H activation pathways mainly governed by sterics. KW - structure elucidation KW - borylene complexes KW - cycloaddition KW - metathesis KW - reaction mechanisms Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257397 VL - 2021 IS - 45 ER - TY - THES A1 - Menche, Dirk T1 - Knipholon und verwandte Phenylanthrachinone T1 - Knipholone and related Phenylanthrachinones N2 - Im Rahmen dieser Arbeit wurde unter Verwendung des 'Lacton-Konzeptes' ein stereoselektiver Zugang zu einem konfigurativ stabilen AB-Biarylfragment von Vancomycin geebnet, wobei verschiedene Schutzgruppenstrategien verfolgt wurden. Weiterhin gelang eine erste, zudem atropselektive Totalsynthese von Knipholon und verwandten Phenylanthrachinonen, die den ersten stereoselektive Zugang zu Biarylanthrachinonen im allgemeinen darstellt. Schließlich wurden neuartige natürlich vorkommende Phenylanthrachinone entdeckt und deren Strukturen aufgeklärt. N2 - During this thesis using the 'lacton concept' a stereoselective approach to the AB biaryl fragment of vancomycin was established requiring the study of different protective group strategies. In addition, a first, moreover atroposelective total synthesis of knipholone and related phenylanthraquinones was achieved, which presents the first stereoselective approach to biarylanthraquinones in general. Finally new types of natural phenylanthraquinones were discovered and their structures elucidated. KW - Knipholon KW - Anthrachinonfarbstoff KW - Stereoselektive Synthese KW - Strukturaufklärung KW - Totalsynthese KW - Lacton-Konzept KW - Strukturaufklärung KW - Vancomycin KW - Knipholon KW - Phenylanthrachinone KW - Gaborochinone A und B KW - Total synthesis KW - Lacton concept KW - structure elucidation KW - Vancomycin KW - Knipholone KW - Phenylanthrachinones KW - Gaboroquinone A und B Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-3029 ER - TY - JOUR A1 - Scherpf, Thorsten A1 - Schwarz, Christopher A1 - Scharf, Lennart T. A1 - Zur, Jana-Alina A1 - Helbig, Andeas A1 - Gessner, Viktoria H. T1 - Ylide-Functionalized Phosphines: Strong Donor Ligands for Homogeneous Catalysis JF - Angewandte Chemie - International Edition N2 - Phosphines are important ligands in homogenous catalysis and have been crucial for many advances, such as in cross-coupling, hydrofunctionalization, or hydrogenation reactions. Herein we report the synthesis and application of a novel class of phosphines bearing ylide substituents. These phosphines are easily accessible via different synthetic routes from commercially available starting materials. Owing to the extra donation from the ylide group to the phosphorus center the ligands are unusually electron-rich and can thus function as strong electron donors. The donor capacity surpasses that of commonly used phosphines and carbenes and can easily be tuned by changing the substitution pattern at the ylidic carbon atom. The huge potential of ylide-functionalized phosphines in catalysis is demonstrated by their use in gold catalysis. Excellent performance at low catalyst loadings under mild reaction conditions is thus seen in different types of transformations. KW - carbanion KW - homogeneous catalysis KW - phosphine ligands KW - structure elucidation KW - ylides Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228551 VL - 57 IS - 39 ER - TY - THES A1 - Schies, Christine Lisa T1 - Totalsynthese von Mbandakamin A und Weiteren Dimeren Naphthylisochinolin-Alkaloiden mit Antiplasmodialer Aktivität sowie HPLC-ECD-Analyse Inhärent Chiraler Metallocorrole T1 - Total Synthesis of Mbandakamin A and Related Naphthylisochinoline-Alkaloids with Antiplasmodial Activities and HPLC-ECD-Analysis of inherent Chiral Metallocorrdes N2 - Tropische Infektionskrankheiten sind noch immer die Haupttodesurache in vielen Ländern der Dritten Welt. Unter ihnen ist Malaria neben der Immunschwächekrankheit AIDS und Tuberkulose am weitesten verbreitet. Laut WHO erkrankten allein im Jahr 2016 rund 216 Millionen Menschen an Malaria und weltweit verstarben 445.000 Menschen an den Folgen dieser Infektion. Solange die Wirksamkeit des Impfstoffs RTS,S/AS01 gegen Malaria noch Schwachstellen aufweist und andere Impfstoff-Kanditaten sich noch in präklinischen Testphasen befinden, ist vor allem die Entwicklung neuer Wirkstoffe, auch im Hinblick auf die rasante Ausbreitung von Resistenzen gegen herkömmliche Medikamente, weiterhin eine dringende Aufgabe. Eine vielversprechende Wirkstoffklasse mit interessanten strukturellen Eigenschaften und einer ungewöhnlichen Biosynthese aus Acetat-Einheiten sind die Naphthylisochinolin-Alkaloide aus den beiden paläotropischen Pflanzenfamilien der Dioncophyllaceae und Ancistrocladaceae. Die Naphthylisochinolin-Alkaloide sind hervozuheben aufgrund ihrer exzellenten Aktivität gegen Plasmodium falciparum, den Erreger der Malaria tropica, sowie wegen ihrer Wirksamkeit gegen Erreger weiterer Krankheiten wie beispielsweise AIDS, Leishmaniose und Afrikanische Trypanosomiasis. Auch im Kampf gegen maligne Erkrankungen wie Leukämie und pankreatischen Krebs werden sie aufgrund ihrer cytotoxischen Eigenschaften als vielversprechende Leitstrukturen betrachtet. Die strukturell beeindruckendsten Naphthylisochinolin-Alkaloide sind die dimeren Mbandakamine, die von unserer Arbeitsgruppe vor einiger Zeit aus einer kongolesischen Ancistrocladus-Liane isoliert wurden. Sie besitzen sieben stereogene Elemente und sind die ersten natürlich vorkommenden Dimere mit einer höchst unsymmetrischen 6',1''-gekuppelten zentralen Biarylachse. Diese impliziert eine außergewöhnlich hohe sterische Hinderung an der zentralen Achse, wie sie noch in keinem anderen dimeren Naphthylisochinolin-Alkaloid gefunden wurde. Verbunden mit ihren bemerkenswerten und vielseitigen pharmakologischen Wirkeigenschaften sind sie ausgesprochen interessante Moleküle für eine synthetische Erschließung. Ziel dieser Arbeit war die erstmalige Totalsynthese von Mbandakamin A und B sowie die Synthese ihrer monomeren Hälften 5-epi-Korupensamin E und 8-O-Methylkorupensamin A. Zudem sollten weitere Naphthylisochinolin-Dimere, die bei der Synthese der Mbandakamine anfallen, isoliert und charakterisiert werden. Alle neuen mono- und dimeren Naphthylisochinoline sollten abschließend am Schweizerischen Tropen- und Public-Health-Institut auf ihre biologische Aktivität getestet werden. Zusätzlich gelang im Rahmen eines Kooperationsprojekts erstmals die stereochemische Charakterisierung des strukturell ganz neuartigen, inhärent chiralen Wolframbiscorrols durch online HPLC-ECD-Analyse in Kombination mit quantenchemischen Rechnungen. N2 - Tropical infectious diseases are still the leading cause of death in developing countries. Among them, malaria is the most widespread one, besides the immunodeficiency syndrome AIDS and tuberculosis. According to the WHO about 216 million people were diagnosed with malaria in 2016, and it was estimated that 445 000 deaths due to malaria occurred globally. As long as vaccinations still show weaknesses in their efficacy or are only in the pre-clinical phase, the development of new drugs is inevitable because of the rapid spread of drug resistance. A promising class of agents with interesting structural properties and an unusual biosynthesis are the naphthylisoquinoline alkaloids from the two palaeotropic plant families of Dioncophyllaceae and Ancistrocladaceae, because not only the naphthalene parts but also the isoquinoline moieties originate from acetate- units. The naphthylisoquinoline alkaloids have attracted attention due to their high activities against Plasmodium falciparum, the pathogen causing malaria tropica, and for their effectiveness against the pathogens of further tropical diseases such as AIDS, leishmaniasis, schistosomiasis and trypanasomiasis. In the fight against malignant diseases such as leukemia and pancreatic cancer, they are also considered as promising lead structures, because of their cytotoxic properties. Structurally most impressive naphthylisoquinoline alkaloids are the dimeric mbandakamines, recently isolated by our group from a Congolese Ancistrocladus liana. The mbandakamines possess seven stereogenic elements and are the first naturally occurring dimers with a highly unsymmetric 6',1''-coupled central biaryl axis. This implies an exceptionally high steric hindrance that has not been found in any other dimeric naphthylisoquinoline alkaloid so far. In combination with their remarkable pharmacological activities, they are extremely interesting synthetic goals. The aim of of the present work was the first synthesis of 5-epi-korupensamine E and 8-O- methylkorupensamine A, which are the two molecular halves of mbandakamines A and B, followed by their phenol-oxidative coupling to give rise to the mbandakamines. Additionally, further mono- and dimeric naphthylisoquinolines obtained en route to the mbandakamines were to be isolated and characterized. Moreover, all new mono- and dimeric naphthylisoquinolines were to be tested for their antiprotozoal activities at the Swiss Tropical and Public Health Institute. In addition,in a cooperation project the stereochemical characterization of an inherently chiral tungsten biscorrole by online-HPLC-ECD analysis in combination with quantum-chemical calculations was achieved for the very first time. KW - Naphthylisochinolin-Alkaloide KW - Corrole KW - Isolierung KW - Natural products KW - Naturstoffe KW - Strukturaufklärung KW - Totalsynthese KW - Malaria KW - isolation KW - structure elucidation KW - total synthesis KW - Naphthylisochinolin-Alkaloide KW - Corrole Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-185012 ER - TY - THES A1 - Seupel, Raina T1 - Antiinfektive und Antitumorale Naphthylisochinolin-Alkaloide: Isolierung und Strukturaufklärung, Totalsynthese und Untersuchungen zum Wirkmechanismus T1 - Antiinfective and Antiturmoral Naphthylisoquinoline Alkaloids: Isolation and Elucidation, Total Synthesis, and Investigations on the Mode of Action N2 - Bedingt durch ihre strukturelle Diversität und biologischen Eigenschaften sind Naturstoffe seit jeher Quelle und Inspiration für Arzneimittel vor allem im therapeutischen Bereich der Onkologie und der Infektionskrankheiten. Ihr einzigartiges pharmakologisches Potenzial wird durch die selektive Interaktion mit einer Vielzahl von Zielmolekülen hervorgerufen. Aufgrund der zentralen Bedeutung von Naturstoffen in der Entdeckung und Entwicklung von neuen Arzneimitteln sind nach wie vor die Isolierung und Strukturaufklärung, die totalsynthetische Darstellung und Derivatisierung sowie die Identifizierung der Zielmoleküle und die Aufklärung des Wirkmechanismus dieser natürlichen Wirkstoffe unabdingbar. Die kleine, aber spannende Klasse der Naphthylisochinolin-Alkaloide, die ausschließlich aus den beiden Pflanzenfamilien der Dioncophyllaceae und der Ancistrocladaceae gewonnen werden, zeichnet sich mit ihren mehr als 200 Vertretern nicht nur durch ihre strukturelle Vielfalt aus, sondern zeigt vor allem pharmakologisch interessante Wirksamkeiten. Neben ausgeprägten In-vitro-Aktivitäten gegen protozoische Erreger wie Leishmanien, Plasmodien und Trypanosomen besitzen die Vertreter dieser einzigartigen Naturstoffklasse nach neuesten Untersuchungen auch vielversprechende antitumorale Aktivitäten. Für deren Weiterentwicklung zu möglichen Arzneistoffen ist es daher unabdingbar, ihr pharmakologisches Potenzial tiefergehend zu untersuchen. Ziel der vorliegenden Dissertation war die Entwicklung totalsynthetischer Zugänge zu biologisch interessanten Naphthylisochinolin-Alkaloiden mit Hilfe unterschiedlicher Synthesestrategien. Ebenfalls sollten durch die Darstellung strukturell vereinfachter Derivate sowie markierter Naturstoffe in Zusammenarbeit mit Kooperationspartnern mögliche Zielmoleküle identifiziert und Beiträge zum Wirkmechanismus untersucht werden. N2 - Due to their structurally diversity and biological properties, natural products have been, for a long time, a source and inspiration for drugs, especially in the therapeutic areas of oncology and infectious diseases. Their unique pharmacological potential is a result of their selective interaction with a variety of target molecules. Owing to the central role of natural products in the discovery and development of new drugs, the isolation, structural elucidation, the total synthesis and derivatization, the identification of target molecules, and investigations on the mode of action of these natural compounds are still essential. The small, yet fascinating class of naphthylisoquinoline alkaloids, which are exclusively obtained from the two plant families of Dioncophyllaceae and Ancistrocladaceae, does not only stand out due to their structural diversity with more than 200 representatives, but also shows pharmacologically interesting activities. In addition to pronounced in vitro activities against protozoan pathogens such as leishmania, plasmodia and trypanosoma, the representatives of this unique class of natural products also show promising antitumoral activities. For their further development as possible drugs, their pharmacological potential has to be investigated in more detail. The aim of the present thesis was the development of total synthetic approaches to biologically interesting naphthylisoquinoline alkaloids by means of different strategies. The synthesis of structurally simplified derivatives and of labeled natural products together with cooperation partners was also intended to identify potential targets and contribute to the mode of action. KW - Naphthylisochinolinalkaloide KW - Organische Synthese KW - Naturstoffe KW - Natural products KW - Totalsynthese KW - Isolierung KW - Strukturaufklärung KW - Wirkmechanismus KW - total synthesis KW - isolation KW - structure elucidation KW - mode of action Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167950 ER - TY - JOUR A1 - Tshitenge, Dieudonné Tshitenge A1 - Feineis, Doris A1 - Mudogo, Virima A1 - Kaiser, Marcel A1 - Brun, Reto A1 - Bringmann, Gerhard T1 - Antiplasmodial Ealapasamines A-C,'Mixed' Naphthylisoquinoline Dimers from the Central African Liana Ancistrocladus ealaensis JF - Scientific Reports N2 - Three unusual heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A-C (1–3), were isolated from the leaves of the tropical plant Ancistrocladus ealaensis J. Léonard. These ‘mixed’, constitutionally unsymmetric dimers are the first stereochemically fully assigned cross-coupling products of a 5,8′- and a 7,8′-coupled naphthylisoquinoline linked via C-6′ in both naphthalene portions. So far, only two other West and Central Ancistrocladus species were known to produce dimers with a central 6,6″-axis, yet, in contrast to the ealapasamines, usually consisting of two 5,8′-coupled monomers, like e.g., in michellamine B. The new dimers 1–3 contain six elements of chirality, four stereogenic centers and the two outer axes, while the central biaryl axis is configurationally unstable. The elucidation of the complete stereostructures of the ealapasamines was achieved by the interplay of spectroscopic methods including HRESIMS, 1D and 2D NMR (in particular ROESY measurements), in combination with chemical (oxidative degradation) and chiroptical (electronic circular dichroism) investigations. The ealapasamines A-C display high antiplasmodial activities with excellent half-maximum inhibition concentration values in the low nanomolar range. KW - structure elucidation KW - stereochemistry KW - Ancistrocladus ealaensis KW - dimers Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170645 VL - 7 IS - 5767 ER - TY - JOUR A1 - Zhang, Chonghe A1 - Liu, Xiaocui A1 - Wang, Junyi A1 - Ye, Qing T1 - A Three-Dimensional Inorganic Analogue of 9,10-Diazido-9,10-Diboraanthracene: A Lewis Superacidic Azido Borane with Reactivity and Stability JF - Angewandte Chemie N2 - Herein, we report the facile synthesis of a three-dimensional (3D) inorganic analogue of 9,10-diazido-9,10-dihydrodiboraantracene, which turned out to be a monomer in both the solid and solution state, and thermally stable up to 230 °C, representing a rare example of azido borane with boosted Lewis acidity and stability in one. Apart from the classical acid-base and Staudinger reactions, E−H bond activation (E=B, Si, Ge) was investigated. While the reaction with B−H (9-borabicyclo[3.3.1]nonane) led directly to the 1,1-addition on N\(_{α}\) upon N\(_{2}\) elimination, the Si−H (Et\(_{3}\)SiH, PhMe\(_{2}\)SiH) activation proceeded stepwise via 1,2-addition, with the key intermediates 5\(_{int}\) and 6\(_{int}\) being isolated and characterized. In contrast, the cooperative Ge−H was reversible and stayed at the 1,2-addition step. KW - E-H bond activation KW - boracycle KW - azido borane KW - lewis superacid KW - structure elucidation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318322 VL - 61 IS - 36 ER -