Rozprawy doktorskie na temat „Isochromans”

Many of the naturally occurring benzoisochromanquinones exhibit notable biological activity, being potential antibiotics or antineoplastic agents. The synthetic work described in this thesis is directed towards the asymmetric synthesis of Quinone A 2, Quinone A 3 and Deoxyquinone A 4, three derivatives of the naturally occurring benzoisochromanquinone aphid pigments, protoaphin-fb, protoaphin-sl and deoxyprotoaphin, respectively. In the first chapter, a comprehensive review of a category of benzoisochromanquinone natural products related to the aphid pigment derivatives is presented, highlighting their structures, occurrence and biological activities. This is followed by a discussion of the isolation and structural elucidation of the aphid pigments themselves. The racemic synthesis of the aphid pigment derivatives 2, 3 and 4, and the asymmetric syntheses of several related naturally occurring benzoisochromanquinones are reviewed in the latter part of the chapter. An approach to the first chiral synthesis of Quinone A 2, Quinone A' 3 and Deoxyquinone A 4, through a key intermolecular reaction between a metal phenolate and a chiral aldehyde, is detailed in Chapter Two. It was first necessary to prepare an aromatic compound which is a suitable precursor to the benzyne 189. The assembly of two different precursors is described, and the yields of their respective conversions to the intermediate benzyne 189 and in situ cycloaddition reaction with 2-methoxyfuran compared. Model studies of the key intermolecular reaction, using 4,5,7-trimethoxynaphthalene-1-ol and the 1-ethoxyethyl ether of (2S)-2-hydroxypropanal, are then presented. This reaction was highly diastereoselective and this was controlled by the choice of the metal. Thus, the product of addition of the titanium phenolate differed from that of the magnesium phenolate only at the newly created chiral centre. Chapter Three deals with the application of the reaction between metal phenolates and chiral aldehydes to intramolecular processes. Firstly, commercially available 2,5-dihydroxyacetophenone was transformed into the differentially protected 5-benzyloxy-2-methoxyacetophenone. This was followed by extension of the side chain by formation of an ether with (S)-ethyl lactate. Ultimately, two diastereomeric optically-pure phenols, each bearing an aldehydic side chain derived from (S)-ethyl lactate, were prepared. These were each treated separately with both titanium tetraisopropoxide and ethyl magnesium bromide and the products of the four reactions examined in detail. In the case of the bromomagnesium phenolates, the yields of cyclized products were poor, and for one of these diastereomeric phenolates the stereoselectivity of cyclization was only average. For the titanium phenolates, high yields of products of intramolecular cyclization were obtained. The diastereoselectivity of the cyclization reaction was only 3:1 in one case, but in the other, which produced the required benzopyran analogous to Quinone A, the cyclization was completely diastereoselective. Thus, the first chiral synthesis of a benzopyranquinone having the same absolute stereochemistry as the enantiomer of Quinone A, i.e., quinone 234, is presented.

Comment peut-on influencer la réactivité chimique ? Dans ce travail de thèse, j’ai tâché de répondre à cette question en explorant la frontière entre la chimie et la physique. Dans un premier temps, en tirant avantage du solvant 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) qui permet souvent une réactivité exotique, qui peut être attribuée à ses exceptionnelles propriétés physiques. Ces dernières font de HFIP une véritable matrice supramoléculaire, qui nous a permis le développement d’une nouvelle méthode pour la synthèse d’isochromanes fonctionnalisés. Ce faisant, une généralité et une simplicité opératoire inédites pour la synthèse de ce motif important furent atteintes. Dans un second temps, j’ai exploré la capacité de l’hybridation lumière-matière, accessible grâce au couplage fort vibrationnel (CFV) de modifier la cinétique de certaines réactions chimiques. Ainsi, en plaçant entre deux miroirs différents réactifs, j’ai étudié l’impact du CFV sur la nucléophilicité ainsi que sur la réactivité Diels-Alder
How can we influence chemical reactivity? Throughout this thesis, I attempted to answer this question by exploring the frontier between chemistry and physics.First, I took advantage of solvent 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) which often unlocks exotic reactivity that can be explained by its extraordinary physical properties. These properties make of HFIP a veritable supramolecular matrix, which allowed the development of a new method for the synthesis of densely functionalized isochromans. This method displayed unprecedented generality, simplicity, and practicality on the way to this pharmacologically important motif.Second, I investigated how light-matter hybridization, accessed through Vibrational Strong Coupling (VSC) could alter the kinetics of some chemical reactions. In practice, by placing different reactants between two mirrors, I studied the impact of VSC on nucleophilicity, as well as on Diels-Alder reactivity

Compte tenu de l’omniprésence des hétérocycles azotés dans de nombreux produits bioactifs, le développement de méthodologies efficaces pour y accéder et les fonctionnaliser constitue un objectif majeur en chimie. Les ynamides représentent des châssis moléculaires intéressants permettant l’accès à divers hétérocycles azotés ou oxygénés. Notre objectif a consisté à étudier la réactivité des ynamides afin de synthétiser des petites bibliothèques de molécules d’intérêt biologiques à partir d’un squelette commun. La mise en oeuvre de méthodologie innovante a été nécessaire en s’attachant à respecter les principes suivants : économie d’atomes, processus catalytique, synthèse en peu d’étapes avec un contrôle de la chimio- et de la régiosélectivité.Dans un premier temps, nous avons étudié la réaction de carbozincation d’ynamides permettant l’accès à divers énamides diversement substitués. Par la suite, l’étude de la réaction de cycloisomérisation des yne-carbamates nous a permis le développement de deux méthodologies avec des sels de zinc (II) ou de rhodium (II) permettant l’accès aux noyaux oxazolones et à ses dérivés. Nos projets se sont ensuite orientés vers l’étude de l’intermédiaire ion cétèniminium, accessible via une activation acide de l’ynamide. Le développement de deux méthodes d’accès aux noyaux 3-amino-isocoumarines a pu être réalisé via l’ajout d’acide de Lewis ou de Brønsted ou via une cyclisation électrophile. Pour finir, un processus tandem de couplage/cycloisomérisation/addition nucléophile a été mis en place afin d’accéder aux noyaux 1H-isochromène
The constant demand for original small molecule collections with promesing therapeutic potential have required the development of new and efficient synthetic methods. Given the nitrogen ubiquity in nature and in life sciences, the aim of this work is the development of original heterocyclic building blocks, originated from the functionalization of ynamide frameworks. Our goal was to study the reactivity of ynamides in order to synthesize from a common skeleton small library of nitrogen or oxygen compounds with biological relevance. The implementation of a new innovative methodology has been necessary, while trying to adhere to the following principles: atom economy, catalytic reaction, fast synthesis in minimal steps, and control of chemo- and regioselectivity.Firstly, we studied the carbozincation reaction of ynamides allowing access to several substituted enamides. Subsequently, cycloisomerization reaction of yne-carbamates has allowed us the development of two novels methodologies using zinc (II) or rhodium (II) salts, which provide access to oxazolone scaffolds. Our research has been studying the keteniminium ion intermediates accessible via an acid activation of ynamide. The development of two methods for the 3-amino-isocoumarin core was achieved via addition of Lewis or Brønsted acid or via electrophilic cyclization. Finally, a tandem coupling / cycloisomerization / nucleophilic addition reaction was carried out in order to prepare 1H-isochromene

Divers silatrienes et alcenyl(bromomethyl)silanes presentant un atome de silicium chiral ont ete synthetises en 4 a 6 etapes a partir de chlorosilanes commerciaux avec des rendements satisfaisants afin d'etudier la selectivite de reactions de diels-alder intramoleculaires et de cyclisations radicalaires intramoleculaires. Des 4-sila-4a,7,8,8a-tetrahydroisochroman-1-ones et des 4-sila-3,4,4a,7,8,8a-hexahydro-2h-isoquinolein-1-ones ont ete preparees diastereoselectivement par reaction de diels-alder intramoleculaire des acrylates, methacrylates et monomethylfumarates de 2-methyl-2-silahexa-3,5-dienyle et des n-benzyl-n-(buta-1,3-dienylsilylmethyl)acrylamides. C'est la cycloaddition de l'acrylate de 2-(2-methoxyphenyl)-2-methyl-2-silahexa-3,5-dienyle catalysee par etalcl#2 a temperature ambiante qui presente la meilleure selectivite: l'un des diastereoisomeres constitue 90% du melange des quatre silatetrahydroisochromanones isole avec un rendement de 74%. Des 4-sila-3,4,4a,5-tetrahydro-2h-isoquinolein-1-ones ont ete preparees diastereoselectivement par reaction de diels-alder a demande electronique inverse des n-benzyl-n-(vinylsilylmethyl)-2-pyranone-6-carboxamides, suivie d'elimination de co#2 par reaction de retro diels-alder. La meilleure selectivite (rapport des diastereoisomeres: 80/20) a ete obtenue avec le compose presentant les groupes cyclohexyle et methyle sur l'atome de silicium. La 4-cyclohexyl-4-methyl-4-sila-3,4,4a,5,6,8a-hexahydro-2h-isoquinolein-1-one-6,8a-carbolactone intermediaire dans cette reaction a pu etre isolee. Le traitement des alcenyl(bromomethyl)silanes par l'hydrure de tributyletain permet de preparer selectivement et avec de bons rendements des silacyclopentanes, des silacyclohexanes et des silacycloheptanes

Cette thèse est composée de deux parties distinctes ayant comme thématique commune, la synthèse d’hétérocycles via la catalyse organométallique.Nous nous sommes intéressés, dans un premier temps, à une voie de synthèse permettant un accès rapide au squelette tétrahydrocyclopenta[c]acridine. Ces composés polyfonctionnalisés sont obtenus très efficacement en seulement trois étapes dans des conditions particulièrement douces. L’étape clé de cette synthèse est une réaction de Pauson-Khand intramoléculaire catalysée au cobalt. Certains composés issus de la famille des tétrahydrocyclopenta[c]acridines présentent une activité d’inhibition sélective envers les kinases dépendantes des cyclines (CDKs), et plus particulièrement la CDK2. Un composé chef de file est identifié, puis grâce aux données de co-Cristallisation avec CDK2 et de modélisation moléculaire, suivi de l’étude des relations structure-Activité, la conception rationnelle d’une deuxième génération de molécules est rendue possible. Le composé le plus avancé présente une CI50 de 300 nM envers CDK2/cyclin A et un excellent profil de stabilité métabolique.Dans un deuxième temps, nous avons étudié et développé une réaction tandem d’addition/cyclisation catalysée par l’argent, avec des nucléophiles carbonés sur des substrats ortho-Alcynylbenzaldéhydes. La stratégie de synthèse conduit à des dérivés 1H-Isochromènes par création de deux nouvelles liaisons (C-C et C-O). Une étude approfondie de la réaction tandem nous a permis d’obtenir une large gamme de dérivés d’isochromènes en mettant en évidence l’influence de différents substituants, portés par le groupement alcyne ou le substrat, ainsi que l’utilisation de différents nucléophiles carbonés (alcynes, aromatiques, hétéroaromatiques). Les limitations de la réaction tandem ont également pu être identifiées
My thesis proJect is organized around two main topics having in common organometallic chemistry and the synthesis of heterocycles.Firstly, we were interested in a methodology for the synthesis of tetrahydrocyclopenta[c]acridines. These compounds are synthesized in three steps from various quinolines. The key step is a cobalt-Catalyzed intramolecular Pauson-Khand reaction. Some compounds of this family exhibit selective Cyclin Dependent Kinases (CDKs) inhibition, particulary against CDK2, in the submicromolar range. A hit compound has been identified, and then using data from co-Crystallization with CDK2 and molecular modeling, followed by the study of structure-Activity relationships, the rational design of a second generation of molecules has been investigated. The most advanced compound has an IC50 of 300 nM against CDK2/cyclin A with an excellent metabolic profile. In the second axis of research, we have studied and developed a new silver-Catalyzed tandem addition/cyclization reaction with carbon nucleophiles. The systems studied are (hetero)aromatics compounds having an aldehyde group and in ortho-Position an alkynyl group. The synthetic strategy leads to 1H-Isochromene derivatives by creating two new bonds. A thorough study of the tandem reaction allowed us to obtain a wide range of isochromene derivatives, highlighting the influence of different substituents carried by the alkyne group or on the (hetero)aromatic substrates; and also to investigate the use of different carbon nucleophiles (alkynes, aromatics and heteroaromatics). The limitations of the tandem reaction have also been identified

Im Rahmen dieser Arbeit wurden vier Phthalocyanine untersucht: Metallfreies-Phthalocyanin (H2Pc), Kupferphthalocyanin (CuPc) und Fluor-substituiertes Phthalocyanin (F4CuPc und F16CuPc). Das Ziel dieser Arbeit ist die Charakterisierung der elektronischen und chemischen Eigenschaften der Grenzflächen zwischen diesen Molekülen und Silizium. Die Moleküle wurden durch organische Molekularstrahldeposition (OMBD) im Ultrahochvakuum auf wasserstoffpassivierte Si(111)-Substrate aufgedampft. Oberflächensensitive Messmethoden wie Photoemissionsspektroskopie (PES), Bremsstrahlung Isochromaten Spektroskopie (BIS oder IPES - Inverse Photoemissionsspektroskopie) und Spektroskopie der Röntgen-Absorptions-Feinstruktur (NEXAFS – Near Edge X-Ray Absorption Fine Structure) wurden zur Charakterisierung eingesetzt. Um eine Zuordnung der verschiedenen Komponenten in PES und IPES zu ermöglichen, wurden Methoden der Dichtefunktionaltheorie zur theoretischen Berechnung eingesetzt. Die Energieniveauanpassung an der Grenzfläche zwischen der organischen Schicht und der H-Si-Grenzfläche, sowie die Transportbandlücke von H2Pc, CuPc, F4CuPc und F16CuPc wurden mit Hilfe von PES und IPES bestimmt. Die NEXAFS-Messungen ermöglichten eine genaue Bestimmung der Molekülorientierung relativ zum Substrat. Die Auswertung der Daten zeigte unterschiedliche Molekülorientierungen in dünnen und dicken Filmen. Diese Änderungen wurden mit dem bandverbiegungsähnlichen Verlauf der HOMO-und LUMO-Positionen in Verbindung gebracht. Zusätzlich zu diesem Verhalten wiesen die Grenzflächen auch einen Grenzflächendipol auf, welcher durch die unterschiedlichen Austrittsarbeiten der Kontaktmaterialien hervorgerufen wird. Der Einfluss des Grads der Flouridierung wird durch eine ähnlichen Zunahme der Elektronenaffinität (EA), der Austrittsarbeit (WF) und der Ionisierungsenergie (IE) bestätigt. Die elektronischen Eigenschaften von Metall/organische-Schicht-Grenzflächen und von organischen Schichten unter Sauerstoffeinfluss wurden mit Hilfe von PES und IPES untersucht. Die Ag/Pc Grenzflächen zeigten eine Mischung aus HOMO-LUMO-Verschiebungen und Grenzflächendipolbildung. An den Ag/H2Pc- und Ag/F16CuPc- Grenzflächen wurde ein Ladungstransferkomplex gebildet. Auf der CuPc-Schicht physisorbiert das Ag lediglich und im Fall von F4CuPc wird Ladung zu Ag transferiert, wobei eine andauernde n-Typ-Dotierung an der Grenzfläche erzeugt wird. In Analogie zum Fall der Pc/H-Si Grenzfläche wiesen die Dipole, die hier gefunden wurden, eine lineare Abhängigkeit von EA, WF und IE auf und können durch die Differenz zwischen den Austrittsarbeiten vorausgesagt werden. Das Verhalten der dicken organischen Schichten unter Sauerstoffeinfluss kann in zwei Gruppen eingeteilt werden. Eine Gruppe, bestehend aus H2Pc und F4CuPc, wies nur schwache Wechselwirkung auf und der Sauerstoff physisorbiert auf der Pc-Schicht. Die beiden anderen Moleküle, CuPc und F16CuPc konnten einer Gruppe starker Wechselwirkung zugeordnet werden. CuPc bildet einen Ladungstransferkomplex mit Sauerstoff und auf F16CuPc wird eine polarisierte Schicht gebildet
In the context of this work four Phthalocyanine were studied: Metal-free Phthalocyanine (H2Pc), Copper Phthalocyanine (CuPc) and fluorine-substituted Phthalocyanine (F4CuPc and F16CuPc). The goal of this work is the electronic and chemical characteristics of the interfaces. The molecules were deposited by organic molecular beam deposition (OMBD) in the ultra high vacuum on hydrogen-passivated Si(111)-Substrate. Surface sensitive techniques such as photoemission spectroscopy (PES), bremsstrahlung isochromate spectroscopy (BIS or IPES - inverse photoemission spectroscopy) and near edge X-ray absorption fine structure spectroscopy (NEXAFS) were used for characterisation. Theoretical computations by density functional theory methods were employed, in order to assign different components in PES and IPES. The energy level alignment at the organic/H-Si interface, as well as the transport gap of H2Pc, CuPc, F4CuPc and F16CuPc were determined by PES and IPES. The NEXAFS measurements determine the exact molecular orientation with respect to the substrate. The evaluation of the data showed different molecular orientation in the thin and thick films. This change was correlated with the band bending like behaviours that emerged at these interfaces. In addition to the band bending like behaviour, the interfaces show also an interface dipole which is driven by the work function difference between the contact materials. The influence of the degree of fluorination is confirmed in the similar increase of the EA, WF and IE. The electronic properties of metal/organic layer interfaces and of organic layer under oxygen influence were examined by PES and IPES. The Ag/Pc interfaces show a mixture of HOMO-LUMO shifts and interface dipole formation. A charge transfer complex is formed in the case of Ag/H2Pc and Ag/F16CuPc interfaces. Ag is physisorbed atop the CuPc. Charge transfers from F4CuPc to Ag creating a continuous n-type doping at the interface. Similar to the Pc/H-Si interfaces the interface dipoles found here show a linear dependence on the EA, WF and IE and can be predicted by the difference in the work functions. The data evaluation of oxygen exposed thick films determined two groups of behaviours. The weak interaction group is represented by H2Pc and F4CuPc, Pcs on which oxygen is physisorbed. The strong interaction group contains the other two molecules CuPc and F16CuPc. CuPc forms a charge transfer complex with oxygen and on top of F16CuPc a polarized layer is formed

Inverse photoemission spectroscopy (IPES) is utilized for determining the unoccupied electron states of materials. It is a complementary technique to the widely used photoemission spectroscopy (PES) as it analyzes what PES cannot, the states above the Fermi energy. This method is essential to investigating the structure of a solid and its states. IPES has a broad range of uses and is only recently being utilized. This thesis describes the setup, calibration and operation of an IPES experiment. The IPES setup consists of an electron gun which emits electrons towards a sample, where photons are released, which are measured in isochromat mode via a photon detector of a set energy bandwidth. By varying the electron energy at the source, a spectrum of the unoccupied density of states can be obtained. Since IPES is not commonly commercially available the design consists of many custom made components. The photon detector operates as a bandpass filter with a mixture of acetone/argon and a CaF2 window setting the cutoff energies. The counter electronics consist of a pre-amplifier, amplifier and analyzer to detect the count rate at each energy level above the Fermi energy. Along with designing the hardware components, a Labview program was written to capture and log the data for further analysis. The software features several operating modes including automated scanning which allows the user to enter the desired scan parameters and the program will scan the sample accordingly. Also implemented in the program is the control of various external components such as the electron gun and high voltage power supply. The new setup was tested for different gas mixtures and an optimum ratio was determined. Subsequently, IPES scans of several sample materials were performed for testing and optimization. A scan of Au was utilized for the determination of the Fermi edge energy and for comparison to literature spectra. The Fermi edge energy was then used in a measurement of indium tin oxide (ITO) determining the conduction band onset. This allowed the determination of the "transfer gap" of ITO. Future experiments will allow further application of IPES on materials and interfaces where characterization of their electronic structure is desired.

碩士
高雄醫學大學
藥學研究所碩士在職專班
92
英文摘要 In this study, 2-allyloxyisovanillin ( 2 ), prepared from isovanillin ( 1 ), was heated at higher temperature ( 180 ℃) to undergo the Claisen rearrangement to furnish 2-allyl-3-hydroxy-4-methoxybenzaldehyde ( 3 ). Based on O-alkylation and reduction ,compound 3 was converted into 3-alkyloxy-2-allyl-4-methoxybenzyl alcohol ( 5 ) in good yields. Followed by the treatment of compound 5 with potassium tert-butoxide to undergo the isomerization of the allylic double bond, and concomitantly to undergo the sp2-endo trigonal intramolecular cyclization, gave a series of new substituted isochromans in moderate yields.

Faculty of Science School of Chemistry 9800165e govendor@aurum.wits.ac.za
Pyranonaphthoquinones are biologically important molecules found in a wide variety of bacteria, microbial fungi and plant species. Their biological activity is proposed to be a consequence of their ability to function as bioreductive alkylating agents. This class of compounds, which include monomeric and dimeric examples, contain the basic naphtho[2,3-c]pyran-5,10-dione skeleton, usually with substituents at the C-1 and C-3 positions of the pyran ring. The aim of the first part of the project was to develop a novel method for the synthesis of enantiomerically pure 5,8-dimethoxy-isochroman-4-ol, which will provide a handle for stereoselectively adding substituents to the C-1 and C-3 positions of the pyran nucleus. In the second part of the project we wished to attempt to synthesize the naturally occurring compound, cardinalin 3, the dimer of ventiloquinone L previously synthesized in the Wits laboratories. The synthesis of the enantiomerically pure isochromanol began with 2,5-dihydroxybenzoic acid, which was subjected to a diallylation followed by a Claisen rearrangement. The phenols were protected by a methylation reaction and the ester moiety was reduced to give (2-allyl-3,6- dimethoxyphenyl)methanol. It was then allylated to produce a suitable precursor for a one pot/two step ruthenium mediated isomerisation/ring closing metathesis reaction to produce 5,8-dimethoxy-1H-isochromene in an overall yield of 47%. It was converted to racemic 5,8-dimethoxy-isochroman-4-ol through a hydroboration-oxidation reaction in a yield of 84%. The separation of the enantiomers was achieved by acetylating the alcohol to form 5,8-dimethoxy-3,4-dihydro-1H-isochromen-4-yl acetate and then a lipase enzyme was used to stereospecifically deacetylate one enantiomer, while leaving the other enantiomer untouched. The second part of the dissertation discusses the progress towards the synthesis of cardinalin 3. This project began with the formation of the C-C biaryl axis starting from 1,3-dimethoxybenzene. The synthesis then continued with the diformylation of the biphenyl to give 2,2’,6,6’-tetramethoxy[1,1′-biphenyl]-3,3′-dicarbaldehyde. This was subjected to a Stobbe condensation and a Friedel-Crafts acylative cyclisation to produce diethyl [4,4′-diacetoxy-6,6′,8,8′-tetramethoxy-7,7′-binaphthalene]-2,2′- dicarboxylate. The synthesis will be continued in the PhD, using methodology previously developed for the formation of the monomer, as well as methodology developed here.

碩士
高雄醫學大學
醫藥暨應用化學系碩士班
104
Isochromenes and related cyclic ether structures can be widely seen in various biologically active compounds and also common structural units in natural products. Therefore, using simple and easy way to obtain what we want is a very important challenge in modern organic synthesis and also caused considerable concern. According to literature most of the structure that contains aldehydes or alcohols together with alkynes to cyclization process. And this process is to make use of transition metal or inorganic complex to catalytic action, then form the structure of cyclic ethers. In today’s development of environmentally conscious towards green chemistry, we used potassium carbonate salt in the process of cyclization reaction can make the formation of isochromene structure. In order to synthesize isochromene structure, we used aldehydes as starting material, synthesis design was carried out using three steps, firstly we use Henry reaction, then using Wacker-type oxidation, and finally K2CO3-promoted intramolecular Michael cyclization successfully synthesis isochromene structure.

碩士
國立中正大學
化學暨生物化學研究所
100
Utilization of α,β-unsaturated aldehydes, olefin nitroalkanes and 1,3-dimethylbarbuturic acid undergo organocatalytic Michael-Knoevenagel-Hetero-Diels-Alder reaction via the one pot multicomponent strategy to synthesis isochromene pyrimidinedione derivatives with excellent diastereoselectivity and enantioselectivity. The structure of product was confirmed by X-ray and NMR analysis.

碩士
國立中山大學
化學系研究所
104
In this research, a new method was discovered to selectively obtain cyclic product under gold catalyst and silver co-catalyst or other co-catalyst. Using 4-methoxybenzyl 2-(phenylethynyl)benzoate and their deriviatives under gold and co-catalyst catalyzed in different solvent at 80 oC to get cyclic product 3-phenyl-1H-isochromen-1-one (isocoumarin), and the 4-(4-methoxybenzyl)-3-phenyl-1H-isochromen-1-one also can be obtain in the same time.

Im Rahmen dieser Arbeit wurden vier Phthalocyanine untersucht: Metallfreies-Phthalocyanin (H2Pc), Kupferphthalocyanin (CuPc) und Fluor-substituiertes Phthalocyanin (F4CuPc und F16CuPc). Das Ziel dieser Arbeit ist die Charakterisierung der elektronischen und chemischen Eigenschaften der Grenzflächen zwischen diesen Molekülen und Silizium. Die Moleküle wurden durch organische Molekularstrahldeposition (OMBD) im Ultrahochvakuum auf wasserstoffpassivierte Si(111)-Substrate aufgedampft. Oberflächensensitive Messmethoden wie Photoemissionsspektroskopie (PES), Bremsstrahlung Isochromaten Spektroskopie (BIS oder IPES - Inverse Photoemissionsspektroskopie) und Spektroskopie der Röntgen-Absorptions-Feinstruktur (NEXAFS – Near Edge X-Ray Absorption Fine Structure) wurden zur Charakterisierung eingesetzt. Um eine Zuordnung der verschiedenen Komponenten in PES und IPES zu ermöglichen, wurden Methoden der Dichtefunktionaltheorie zur theoretischen Berechnung eingesetzt. Die Energieniveauanpassung an der Grenzfläche zwischen der organischen Schicht und der H-Si-Grenzfläche, sowie die Transportbandlücke von H2Pc, CuPc, F4CuPc und F16CuPc wurden mit Hilfe von PES und IPES bestimmt. Die NEXAFS-Messungen ermöglichten eine genaue Bestimmung der Molekülorientierung relativ zum Substrat. Die Auswertung der Daten zeigte unterschiedliche Molekülorientierungen in dünnen und dicken Filmen. Diese Änderungen wurden mit dem bandverbiegungsähnlichen Verlauf der HOMO-und LUMO-Positionen in Verbindung gebracht. Zusätzlich zu diesem Verhalten wiesen die Grenzflächen auch einen Grenzflächendipol auf, welcher durch die unterschiedlichen Austrittsarbeiten der Kontaktmaterialien hervorgerufen wird. Der Einfluss des Grads der Flouridierung wird durch eine ähnlichen Zunahme der Elektronenaffinität (EA), der Austrittsarbeit (WF) und der Ionisierungsenergie (IE) bestätigt. Die elektronischen Eigenschaften von Metall/organische-Schicht-Grenzflächen und von organischen Schichten unter Sauerstoffeinfluss wurden mit Hilfe von PES und IPES untersucht. Die Ag/Pc Grenzflächen zeigten eine Mischung aus HOMO-LUMO-Verschiebungen und Grenzflächendipolbildung. An den Ag/H2Pc- und Ag/F16CuPc- Grenzflächen wurde ein Ladungstransferkomplex gebildet. Auf der CuPc-Schicht physisorbiert das Ag lediglich und im Fall von F4CuPc wird Ladung zu Ag transferiert, wobei eine andauernde n-Typ-Dotierung an der Grenzfläche erzeugt wird. In Analogie zum Fall der Pc/H-Si Grenzfläche wiesen die Dipole, die hier gefunden wurden, eine lineare Abhängigkeit von EA, WF und IE auf und können durch die Differenz zwischen den Austrittsarbeiten vorausgesagt werden. Das Verhalten der dicken organischen Schichten unter Sauerstoffeinfluss kann in zwei Gruppen eingeteilt werden. Eine Gruppe, bestehend aus H2Pc und F4CuPc, wies nur schwache Wechselwirkung auf und der Sauerstoff physisorbiert auf der Pc-Schicht. Die beiden anderen Moleküle, CuPc und F16CuPc konnten einer Gruppe starker Wechselwirkung zugeordnet werden. CuPc bildet einen Ladungstransferkomplex mit Sauerstoff und auf F16CuPc wird eine polarisierte Schicht gebildet.
In the context of this work four Phthalocyanine were studied: Metal-free Phthalocyanine (H2Pc), Copper Phthalocyanine (CuPc) and fluorine-substituted Phthalocyanine (F4CuPc and F16CuPc). The goal of this work is the electronic and chemical characteristics of the interfaces. The molecules were deposited by organic molecular beam deposition (OMBD) in the ultra high vacuum on hydrogen-passivated Si(111)-Substrate. Surface sensitive techniques such as photoemission spectroscopy (PES), bremsstrahlung isochromate spectroscopy (BIS or IPES - inverse photoemission spectroscopy) and near edge X-ray absorption fine structure spectroscopy (NEXAFS) were used for characterisation. Theoretical computations by density functional theory methods were employed, in order to assign different components in PES and IPES. The energy level alignment at the organic/H-Si interface, as well as the transport gap of H2Pc, CuPc, F4CuPc and F16CuPc were determined by PES and IPES. The NEXAFS measurements determine the exact molecular orientation with respect to the substrate. The evaluation of the data showed different molecular orientation in the thin and thick films. This change was correlated with the band bending like behaviours that emerged at these interfaces. In addition to the band bending like behaviour, the interfaces show also an interface dipole which is driven by the work function difference between the contact materials. The influence of the degree of fluorination is confirmed in the similar increase of the EA, WF and IE. The electronic properties of metal/organic layer interfaces and of organic layer under oxygen influence were examined by PES and IPES. The Ag/Pc interfaces show a mixture of HOMO-LUMO shifts and interface dipole formation. A charge transfer complex is formed in the case of Ag/H2Pc and Ag/F16CuPc interfaces. Ag is physisorbed atop the CuPc. Charge transfers from F4CuPc to Ag creating a continuous n-type doping at the interface. Similar to the Pc/H-Si interfaces the interface dipoles found here show a linear dependence on the EA, WF and IE and can be predicted by the difference in the work functions. The data evaluation of oxygen exposed thick films determined two groups of behaviours. The weak interaction group is represented by H2Pc and F4CuPc, Pcs on which oxygen is physisorbed. The strong interaction group contains the other two molecules CuPc and F16CuPc. CuPc forms a charge transfer complex with oxygen and on top of F16CuPc a polarized layer is formed.

This thesis contains six chapters and the research presented within focuses on three parts. The first part (chapter one to three) was the isolation of antibacterial and antioxidant mushroom metabolites, and the synthesis towards analogues of discovered natural products. The following part (chapter four) was to assess antioxidant activities of synthetic compounds and investigate their SAR (structure-activity relationship), by use of a developed DPPH assay. The last part (chapter five to six) was the discovery of an abiotic halogenation reaction among a class of fungal metabolites, azaphilones. A series of their synthetic analogues were applied as model compounds to understand the mechanism of the discovered unusual and facile non-enzymatic nucleophilic halogenation reaction. Chapter one is a review of antioxidants in mushrooms. The components with antioxidant activities discovered from mushrooms were summarised by their chemical structures and representative samples were listed. In addition, the potential mechanisms of those antioxidants were described in this chapter. In chapter two, extracts of 20 mushrooms from PNG (Papua New Guinea) were screened against both Gram-positive and Gram-negative bacteria, six of them were chosen as chemical survey candidates for their strong antibacterial activities. Extracts of 37 PNG mushrooms were screened for their antioxidant using a modified DPPH assay, 14 of them were chosen as chemical survey candidates based on their antioxidant capacities. In chemical examination guided by bioactivity, five natural products including two novel furan fatty acids (2.1-2.2) and three known compounds, i.e. grifolin (2.3), grifolic acid (2.4) and grifolic acid methyl ether (2.5), were isolated from four selected mushroom samples. Chapter three described the synthetic efforts towards analogues of three isolated antioxidant fungal metabolites (2.3-2.5). Inspired by 15 synthetic targets, a short and versatile general synthetic route was established to deliver 40 compounds possessing structures related to the natural products. Based on these structures, a compound library was established for antioxidant assessment in the following SAR research. The synthetic work resulted in the preparation of 33 novel structures. In chapter four, various antioxidant assays and their working mechanisms were reviewed, as well as their corresponding advantages and drawbacks. A developed DPPH assay was optimised to offer an accurate and reproducible antioxidant evaluation for SAR research in the achieved compound library. The results indicated that a structure with an aromatic ring to be allylated with a carbon chain in addition to the presence of phenols, is required to show an antioxidant activity, and the increased length of a carbon chain (more prenyl units) enhances the antioxidant activity. Chapter five focused on naturally occurring organohalogen compounds with biotic origins. The representative halogenated natural products with a variety of bioactivities were categorised following a chemical structural classification as well as a bioactive classification, to showcase both their structural diversity and bioactive variety. The biosynthetic mechanisms of halogenated natural products were reviewed in this chapter. Chapter six detailed the investigation of a novel halogenation reaction that was discovered to be occurring with some azaphilone fungal metabolites, for example the conversion of (+)-deschlorosclerotiorin (6.2) into (+)-sclerotiorin (6.1). Various non-halogenated model compounds with an azaphilone core structure were created to shed light on the authenticity of numerous halogenated azaphilones reported as natural products. The ensuing synthetic work resulted in an efficient general procedure producing the required targets. The following investigation of the halogenation revealed a novel, facile, non-enzymatic nucleophilic reaction and its proposed mechanism is discussed. The synthetic efforts resulted in the creation of 22 novel structures.