Die Einleitung gibt einen kurzen Überblick über die Bedeutung von Piperidinalkaloiden und im speziellen wird kurz auf das pharmakologische Potential mariner Piperidinalkaloide eingegangen. Anschließend wird die Substanzklasse der „Pseudodistomine“ vorgestellt, gefolgt von einer Übersicht bereits literaturbekannter Synthesemöglichkeiten. Das primäre Ziel der vorliegenden Arbeit war die Entwicklung eines neuen stereoselektiven Zugangs zum all cis substituierten Grundkörper der Pseudodistomine C und E über die Kaskade einer Tandem Wittig-[3+2]-Cycloaddition. Weiterhin sollten Möglichkeiten ausgelotet werden, um hieran die Seitenkette des Pseudodistomins E aufbauen zu können, um erstmals eine Totalsynthese dessen zu ermöglichen. / The introduction gives a short overview of the importance of piperidine alkaloids and especially of the pharmacological potential of marine piperidine alkaloids. Then the „pseudodistomines“ are introduced, followed by a summary of established possibilities of their syntheses. On the one hand the primary aim of the work was the deployment of a new stereoselective synthetic pathway to the all cis substituted heterocyclic core of the Pseudodistomin C and E via a cascade of the „tandem Wittig-[3+2]-cycloaddition reaction“. Further on there were different possibilities evaluated to lock the side chain of the Pseudodistomine E to the heterocyclic core, in order to allow the first total synthesis.

La structure de l’acide kojique et sa réactivité permet d’effectuer des transformations conduisant à la synthèse de composés polycycliques différents et structurellement très diversifiés. Ces hétérocycles sont obtenus en plusieurs étapes en s’appuyant sur des réactions typiques telles que des cycloadditions [5+2], Diels-Alder, [5+2]/[4+2] tandem, des réactions à 3 composantes ou encore l’utilisation de lithiens. L’utilisation d’appareillages spécifique tels que un réacteur micro-ondes et un synthétiseur en flux continue permettent l’obtention des molécules ciblées d’une façon plus spécifique et efficace. Les chimiothèques de molécules obtenues peuvent dès lors être testé pour une éventuelle activité biologique envers diverses structures. / The structure of kojic acid and its reactivity give the opportunity to make tranformations leading to the synthesis of different polycyclic compounds and structurally diversified. These heterocycles are obtained in several steps by typical reactions like [5+2] cycloaddtions, Diels-Alder reactions, tandem [5+2]/[4+2] cycloadditions, 3 compounds reactions or the use of lithiens. The use of specific equipments like microwave equipment and continuous-flow equipment give the opportunnity to obtain target molecules. Compounds libraries will be test for a biological activity.

Thesis advisor: Marc L. Snapper / Chapter 1: The design of a novel first aid smart fabric that is linked to a biologically active molecule through an event specific cleavable linker is described. Successful functionalization of a cellulose filter paper fabric mimic and the synthesis of a linker which is potentially selectively cleavable in the presence of blood have been achieved. Chapter 2: Synthetic studies towards the total synthesis of Torilin, a sesquiterpene guaiane natural product with interesting biological activities are described. The synthesis of the hydroazulene core of Torilin is accomplished through a cyclopropanation/ Lewis acid mediated fragmentation of a highly functionalized polycyclic system which is rapidly accessed through the intramolecular cycloaddition of cyclobutadiene. / Thesis (MS) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Marc L. Snapper / Tandem Reactions have proven themselves to be useful reactions for the synthesis of highly complex materials. Ruthenium alkylidenes are shown to be useful precursors for the development of new tandem processes. First, a new tandem metathesis/hetero-Pauson-Khand process is developed using Grubbs' second generation catalyst. Next, various metatheis/olefin isomerization processes are explored. / Thesis (PhD) — Boston College, 2009. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Marc L. Snapper / Intramolecular [2+2] photocycloadditions have been studied: (i) Previous studies in our group have demonstrated that there is a regiochemical dependence of intramolecular [2+2] photocycloadditions on the solvent employed. In order to understand the generality of hydrogen bonding effects of photochemical reactions of β-hydroxyl enones, we examined the photochemical outcome of enones with both acyclic and cyclic olefin tethers. (ii) An application of an intramolecular [2+2] photocycloaddition/ fragmentation strategy to form 5-8-5 ring systems has been demonstrated toward the synthesis of the natural product cycloaraneosene. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

O (-)-?-bisabolol é um produto natural abundante na natureza, possui atividades biológicas reconhecidas, que o torna extremamente interessante para as indústrias de cosméticos e fármacos. Este trabalho tem como objetivo à preparação de novos compostos com possíveis aplicações biológicas, agregando valor ao produto natural. Durante as transformações procura-se trabalhar com metodologias ecologicamente corretas (Green Chemistry). O trabalho foi dividido em 4 (quatro) partes principais: oxidação, cicloadição, alquilação e acetilação. A oxidação alílica do (-)-?-bisabolol usando trióxido de cromo (CrO3) forneceu o Deodarone (tetraidro-2,2,6-trimetil-6-(4-metil-3-cicloexen-1-il)-4H-piran-4-ona) com 45,3% de rendimento. A cicloadição [1+2] entre diclorocarbeno e o (-)-?-bisabolol usando CETABr ou KF/Al2O3 originou o 4-(2,2-dicloro-3,3-dimetilciclopropil)-2- (7,7-dicloro-6-metilbiciclo[4.1.0]hept-3-il)-2-butanol com rendimentos de 92% e 97% respectivamente. A alquilação do álcool benzílico com o produto resultante da cicloadição gerou o 4-((2,2-bis(benzilóxi)-3,3-dimetilciclopropil)-2-(7,7- bis(benzilóxi))-6-metillbiciclo[4.1.0]heptan-3-il)butan-2-ol, o rendimento obtido foi de 92%. A epoxidação do (-)-?-bisabolol forneceu o Óxido de Bisabolol B: 1-metil- 1-[5-(4-metil-3-cicloexenil)tetraidro-2-furanil]etil álcool com rendimento de 30%. A acetilação do (-)-?-bisabolol utilizando DMAP ou ZnCl2 forneceu o 2-acetil-(S)-2- metil-2-((R)-4-metillciclohex-3-enil)hept-5-eno com rendimentos de 72,6% e 76,5% respectivamente. Os resultados obtidos foram bastante promissores e podem ser expandidos para trabalhar com outros grupos de moléculas com atividades biológicas. Todos os compostos foram caracterizados por RMN13C (apt). / The (-)-?-bisabolol is a natural product abundant in nature, it has recognized biological activities, which makes it very interesting for the cosmetic and pharmaceutical products. This work aims to prepare new compounds with potential biological applications, adding value to natural product. During the transformation we seek to work with eco-friendly methodologies (Green Chemistry). The work was divided into four (4) main parts: oxidation, cycloaddition, alkylation and acetylation. The allylic oxidation of (-)-?-bisabolol using chromium trioxide (CrO3) provided Deodarone (tetrahydro-2,2,6-trimethyl-6-(4-methyl-3- cicloexen-1-yl)-4H-pyran-4-one) with 45,3% yield. The cycloaddition [1+2] between dichlorocarbene and (-)-?-bisabolol using CETABr or KF/Al2O3 afforded the 4 - (2,2-dichloro-3 ,3-dimethylcyclopropyl) -2 - (7,7-dichloro-6-methylbicyclo [4.1.0] hept-3-yl)-2-butanol with yields of 92% and 97% respectively. Alkylation of benzyl alcohol with the product resulting from cycloaddition generated the 4-(2,2-bis (benzyloxi)-3,3-dimethylcyclopropil)-2-(7,7-bis(benzyloxi)) - 6 - methylbicycle[4.1.0] heptan-3-il)butan-2-ol, the yield was 92%. The epoxidation of (-)-?-bisabolol provided the Bisabolol Oxide B: 1-methyl-1-[5- (4-methyl-3-cicloexenil) tetrahydro- 2-furanyl] ethyl alcohol with yield of 30%. Acetylation of (-)-?-bisabolol using DMAP or ZnCl2 gave the 2-acetyl-(S)-2-methyl-2-((R)-4-metillciclohex-3-enyl) hept- 5-en with yields of 72,6% and 76,5% respectively. The results were very promising and can be expanded to work with others groups of molecules with biological activities. All compounds were characterized by RMN 13C (apt).

X-ray crystallography is an important analytical method for the characterisation of materials in the solid state. During the last decade, it has become important as a tool in the new field of photocrystallography. This combines both crystallography and photochemistry and is used to monitor the formation of light-induced metastable and transient species, so that structural information can be obtained during the change of a material. This is an important area of research as solid state chemistry can display new phenomena and reveal properties that are not possible in solution. Chapter 1 of this thesis commences with a brief introduction to the different methods used to achieve and measure the excitation within crystalline compounds, while Chapter 2 contains an introduction into diffraction methods. In Chapters 3-5 new photocrystallographic studies were performed on two series of compounds. The first one consists of a systematic study on metal complexes with different pyridylethylene ligands. The focus was to align complexes in the solid state so that they can undergo photo induced cycloaddition reactions. These solid state reactions are important as they present “green synthetic chemistry”. The second study involves the photoinduced linkage isomerisation of [Ni(L)2(NO2)2] complexes. Structural characterisation shows that the NO2 ligands change their coordination mode when irradiated with light of different wavelengths. Conditions for the metastable isomerisation were optimised by altering temperature and wavelengths. In Chapters 6 and 7 a systematic study of structural changes in a series of lanthanide complexes and their use as triboluminescence materials, is described. The proposed mechanism of triboluminescence for these complexes is discussed. To summarise, in this thesis, systematic investigations have been carried out in different aspects of crystallography using appropriate series of compounds. The nature of and the conditions required for the change to occur within the solid state have been established.

O (-)-?-bisabolol é um produto natural abundante no Brasil. É extraído de várias espécies de plantas. Possui atividades biológicas reconhecidas, que o torna extremamente interessante para as indústrias de cosméticos e fármacos. O trabalho de pesquisa tem como objetivo principal sua modificação buscando, com isso, melhorar as atividades biológicas ou agregar novas potencialidades biológicas. Durante estas transformações procura-se, principalmente, empregar metodologias ecologicamente corretas (Green Chemistry). O trabalho foi dividido em 3 (três) partes principais: Aminoredução, oxidação e cicloadição. A primeira parte consiste na preparação da imina (N-benzilfenilmetanoamina) e transformação, da mesma, em uma amina secundária, através de aminação redutiva. Na segunda, oxidação das aminas secundárias e do bisabolol e, na terceira, estudo das reações de cicloadições. As oxidações das aminas secundárias (dibenzilamina e 1,2,3,4-tetraidroisoquinolina) forneceram as nitronas correspondentes (N-óxido de N-benzilidenobenzilamina e N-óxido de 3,4-diidroisoquinolina). A oxidação (epoxidação) do Bisabolol forneceu uma mistura de óxidos de Bisabolol: Óxido de Bisabolol - B: 1-metil-1-[5-(4-metil-3-cicloexenil)tetraidro-2-furanil]etil álcool e Óxido de Bisabolol - A: (3S)-2,2,6-trimetil-6-(4-metil-3-cicloexenil)tetraidro-2H-3-piranol. A oxidação alílica do Bisabolol, forneceu o tetraidro-2,2,6-trimetil-6-(4-metil-3-cicloexen-1-il)-4H-piran-4-ona. A cicloadição [1+2] entre diclorocarbeno e o bisabolol originou o 4-(2,2-dicloro-3,3-dimetilciclopropil)-2-(7,7-dicloro-6-metilbiciclo [4.1.0]hept-3-il)-2-butanol. A reação de cicloadição [2+3] entre a nitrona (N-óxido de 3,4-diidroisoquinolina) e o dipolarófilo (butil vinil éter) forneceu a isoxazolidina 1,5,6,10b-tetraidro-2H-isoxazolol[3,2-a]isoquinolina-2-il butil éter. / The (-)-?-bisabolol is a natural product available in a large quantity in Brazil. It is extracted of several specimens of trees and has recognized biological activity that made it a so interesting product for cosmetic and pharmaceutic industries. The research has as mean goal the modification of (-)-?-bisabolol a natural product. The modification has intended, improve the biological activity or create new biological activity. The methods applied always consider condition to protect the environment (Green Chemistry). The research has three main parts: amino reduction, oxidation and cycloaddition. The first part based on the reaction to synthesize the imines (N-benzylphenilmethanoamine) and with the amine reduction synthesis the secondary amine. A second part was oxidizing the secondary amines and bisabolol. The third part is a research about cycloaddition. The amines oxidation (dibenzylamine e 1,2,3,4-tetrahydroisoquinoline) gave the nitrones [N-benzylidenebenzylamine N-oxide and 3,4-dihydroisoquinoline N-oxide] respectively. The Bisabolol oxidation (epoxidation reaction) gave a mix of bisabolol oxide: The Bisabolol oxide B, 1-methyl-1-[5-(4-methyl-3-ciclohexenyl)tetrahydro-2-furanyl]ethyl alcohol and The Bisabolol oxide A, (3S)-2,2,6-trimethyl-6-(4-methyil-3-ciclohexenyl) tetrahydro-2H-3-piranol. The alilic oxidation from Bisabolol also was achieved and gave the tetrahydro-2,2,6-trimethyl-6-(4-methyl-3-cyclohexen-1-yl)-4H-pyran-4-one. The cycload-dition [1+2] between diclorocarbene and bisabolol gave, 4-(2,2-dicloro-3,3-dimethylciclopropil)-2-(7,7-dicloro-6-methylbiciclo[4.1.0]hept-3-yl)-2-butanol. The cycloaddition [2+3] with nitrones (3,4-dihydroisoquinoline N-oxide) and dipolarophile (butyl vinyl ether) gave the isoxazolidine 1,5,6,10b-tetrahydro-2H-isoxazolol[3,2-a]isoquinoline-2-yl butyl ether.

O (-)-?-bisabolol é um produto natural abundante no Brasil. É extraído de várias espécies de plantas. Possui atividades biológicas reconhecidas, que o torna extremamente interessante para as indústrias de cosméticos e fármacos. O trabalho de pesquisa tem como objetivo principal sua modificação buscando, com isso, melhorar as atividades biológicas ou agregar novas potencialidades biológicas. Durante estas transformações procura-se, principalmente, empregar metodologias ecologicamente corretas (Green Chemistry). O trabalho foi dividido em 3 (três) partes principais: Aminoredução, oxidação e cicloadição. A primeira parte consiste na preparação da imina (N-benzilfenilmetanoamina) e transformação, da mesma, em uma amina secundária, através de aminação redutiva. Na segunda, oxidação das aminas secundárias e do bisabolol e, na terceira, estudo das reações de cicloadições. As oxidações das aminas secundárias (dibenzilamina e 1,2,3,4-tetraidroisoquinolina) forneceram as nitronas correspondentes (N-óxido de N-benzilidenobenzilamina e N-óxido de 3,4-diidroisoquinolina). A oxidação (epoxidação) do Bisabolol forneceu uma mistura de óxidos de Bisabolol: Óxido de Bisabolol - B: 1-metil-1-[5-(4-metil-3-cicloexenil)tetraidro-2-furanil]etil álcool e Óxido de Bisabolol - A: (3S)-2,2,6-trimetil-6-(4-metil-3-cicloexenil)tetraidro-2H-3-piranol. A oxidação alílica do Bisabolol, forneceu o tetraidro-2,2,6-trimetil-6-(4-metil-3-cicloexen-1-il)-4H-piran-4-ona. A cicloadição [1+2] entre diclorocarbeno e o bisabolol originou o 4-(2,2-dicloro-3,3-dimetilciclopropil)-2-(7,7-dicloro-6-metilbiciclo [4.1.0]hept-3-il)-2-butanol. A reação de cicloadição [2+3] entre a nitrona (N-óxido de 3,4-diidroisoquinolina) e o dipolarófilo (butil vinil éter) forneceu a isoxazolidina 1,5,6,10b-tetraidro-2H-isoxazolol[3,2-a]isoquinolina-2-il butil éter. / The (-)-?-bisabolol is a natural product available in a large quantity in Brazil. It is extracted of several specimens of trees and has recognized biological activity that made it a so interesting product for cosmetic and pharmaceutic industries. The research has as mean goal the modification of (-)-?-bisabolol a natural product. The modification has intended, improve the biological activity or create new biological activity. The methods applied always consider condition to protect the environment (Green Chemistry). The research has three main parts: amino reduction, oxidation and cycloaddition. The first part based on the reaction to synthesize the imines (N-benzylphenilmethanoamine) and with the amine reduction synthesis the secondary amine. A second part was oxidizing the secondary amines and bisabolol. The third part is a research about cycloaddition. The amines oxidation (dibenzylamine e 1,2,3,4-tetrahydroisoquinoline) gave the nitrones [N-benzylidenebenzylamine N-oxide and 3,4-dihydroisoquinoline N-oxide] respectively. The Bisabolol oxidation (epoxidation reaction) gave a mix of bisabolol oxide: The Bisabolol oxide B, 1-methyl-1-[5-(4-methyl-3-ciclohexenyl)tetrahydro-2-furanyl]ethyl alcohol and The Bisabolol oxide A, (3S)-2,2,6-trimethyl-6-(4-methyil-3-ciclohexenyl) tetrahydro-2H-3-piranol. The alilic oxidation from Bisabolol also was achieved and gave the tetrahydro-2,2,6-trimethyl-6-(4-methyl-3-cyclohexen-1-yl)-4H-pyran-4-one. The cycload-dition [1+2] between diclorocarbene and bisabolol gave, 4-(2,2-dicloro-3,3-dimethylciclopropil)-2-(7,7-dicloro-6-methylbiciclo[4.1.0]hept-3-yl)-2-butanol. The cycloaddition [2+3] with nitrones (3,4-dihydroisoquinoline N-oxide) and dipolarophile (butyl vinyl ether) gave the isoxazolidine 1,5,6,10b-tetrahydro-2H-isoxazolol[3,2-a]isoquinoline-2-yl butyl ether.

Das Ziel dieser Arbeit war die Herstellung von Diamantmaterialien, deren Oberflächen mit Alkinen, Aziden oder Aldehyden modifiziert waren. Diese funktionellen Gruppen sollten die einfache Anbindung verschiedener katalytisch aktiver Systeme mit Hilfe der 1,3-dipolaren Cycloaddition nach Huisgen bzw. Iminbildung ermgöglich. Da in einer vorangegangenen Arbeit Hinweise darauf gefunden wurde, dass die hochgradig funktionalisierte Oberfläche von Detonationsnanodiamant dazu in der Lage ist, die Aktivität von immobilisierten Katalysatoren zu behindern. Darum wurde in dieser Arbeit verglichen, ob die Verwendung von starren Linkern auf Tolanbasis einen Vorteil gegenüber ihren flexiblen Gegenstücken liefert. Dazu wurde für jede der oben genannten Funktionalisierungsarten je ein Diamantmaterial mit flexibler sowie mindestens eines mit unbiegsamer Verbindungseinheit hergestellt und getestet. Dadurch konnte das Konzept der starren Linker für Enzyme bestätigt werden und es wurde eine signifikant höhere Aktivität erhalten, als wenn flexible Anbindungsbrücken verwendet wurden. Bei Organokatalysatoren und metallorganischen Systemen konnten jedoch keine erfolgreichen Katalysen durchgeführt werden. / The aim of this work was the production of diamond materials whose surfaces were modified either with alkynes, azides, or aldehydes. These functional groups were supposed to allow the simple immobilisation of catalytically active systems via 1,3-dipolar cycloadditions or imine formation, respectively. In a previous publication, it was found that the highly functionalised surface of detonation nanodiamond can reduce the activity of immobilised catalysts. In this work, it was therefore investigated whether the use of rigid linkers based on tolane derivatives would be advantageous when compared to their flexible counterparts. For this purpose, at least one example for both cases was produced for each of the above mentioned functional groups. Test results showed that the concept of the rigid linkers was successful for the immobilisation of enzymes, for which a significantly higher activity was detected when compared to flexible linkers. However, for organocatalysts and metal organic systems successful catalysis was not achieved.