This study was aimed at the development of novel CB1 cannabinoid receptor antago­nists that may have clinical applications for the treatment of cannabinoid and psychostimulant addiction. The rationale for the design for our target was to incorporate a bioisosteric 1,2,3-triazole ring into the vicinal diaryl group revealed in the prototypical antagonist/inverse agonist SR141716 (Rimonabant) that was pre­sumed to interact with a unique region in the CB1 receptors. Based on our prelimi­nary results we identified a novel series of 1,2,3-triazole ester and keto deriva­tives as lead compounds for biological evaluation. Here in the design rationale, syn­thesis and CB1 receptor affinity for a series of 4,5-diaryl-1-substituted-1,2,3-triazoles of ester and ketones is described. These derivatives were synthesized via a one-pot regiospecific click/acylation reaction sequence from 1-azido-2,4-dichlorobenzene and commercially available arylacetylenes. From the structure-activity studies the 5-(4-chlorophenyl) congeners exhibited the most potent CB1 receptor affinities relative to other 5-(substituted-phenyl) moieties. The 1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-propylcarbonyl-1,2,3-triazole (­31a) was found to be the most potent (Ki = 4.6 nM) CB1 receptor ligand of the series and exhibited high CB1 selectivity (CB2/CB1 = 417). The triazole ester 31a was further characterized as a cannabinoid antagonist in locomotor-activity studies by blocking the locomotor-reducing effects of cannabinoid agonist WIN55,212-2. In addition, unlike the prototypical cannabinoid antagonist SR141716A (Rimonabant), the triazole ester 31a did not exhibit increased activity in locomotor activ­ity studies, thus indicating the potential for a neutral antagonist profile.

The research investigations presented herein are concerned with the syntheses and applications of arylboronic acids and their derivatives; with a particular focus on their accessibility or utility in certain of the most significant modern transition metal-catalysed reactions to involve organoborons. Chapter 1 provides an introduction to the field of organoboron chemistry, from its roots employing borane and related highly reactive derivatives for uncatalysed hydroboration of olefins and acetylenes, to the modern classes of organoboron reagents of the greatest significance to the related contemporary transition metal-catalysed methodologies. Furthermore particular emphasis is placed on the discussion of arylboronic acids, their synthesis, and application to transition metal catalysis as a result of their propensity to undergo useful transmetallation events. Chapter 2 details the use of a commercially available sulfonated monophosphine ligand in the rhodium-catalysed 1,2-addition reaction employing aryl aldehydes and arylboronic acids in aqueous media. The high and continued activity of the catalytic complex is demonstrated by it being successfully recycled five consecutive times in the arylation reaction of an aryl aldehyde; as well as being active for the arylations of more sterically demanding aryl methyl ketone substrates. Chapter 3 details the design and synthesis of a novel bench-stable azidomethylene substituted arylboronate ester. The reactivity of this compound and a related analogue in both the coppercatalysed azide alkyne cycloaddition reaction and the Suzuki coupling reaction are detailed, culminating in the proof-of-concept use of such versatile synthetic building blocks in the synthesis of a drug-substance derivative. Chapter 4 details alternative synthetic approaches to that used in Chapter 3 in order to access bifunctional azidomethylene substituted arylboronate esters. In particular the application of Miyaura borylation of arylhalides bearing benzylic azides is addressed as a means to rapidly access substrates which are otherwise shown to be incompatible with classical s-block synthetic intermediates.

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2017-11-08T13:12:56Z No. of bitstreams: 1 AmandaCarolineMarquesSa??deTese2016.pdf: 1482640 bytes, checksum: 98c7088a3903d189fcf2c6a44b4fcdc7 (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2017-11-09T11:04:49Z (GMT) No. of bitstreams: 1 AmandaCarolineMarquesSa??deTese2016.pdf: 1482640 bytes, checksum: 98c7088a3903d189fcf2c6a44b4fcdc7 (MD5) / Made available in DSpace on 2017-11-09T11:04:49Z (GMT). No. of bitstreams: 1 AmandaCarolineMarquesSa??deTese2016.pdf: 1482640 bytes, checksum: 98c7088a3903d189fcf2c6a44b4fcdc7 (MD5) Previous issue date: 2016-11-01 / Bacteria are becoming resistant to a growing number of conventional antibiotics at a worrisome rate. Therefore, there is an increasing demand for new antimicrobial therapeutics. Antimicrobial peptides (AMPs) are one of promising alternatives for conventional antibiotics and are thought to be less likely to induce resistance. AMPs have been coupled to molecular scaffolds for biomedical applications such as hydrogels for wound dressings and covering implants. Here AMPs were chemically conjugated to the CR4 hydrophilic polymers. The CPF_C1 is a short peptide isolated from Xenopus clivii, the original sequence was modified one called LCPF_C1, aiming to create some distance between the first glycine and the azide added on the N terminus (on the coupled sequence). The conjugation between the AMP and the CR4 polymer used a click chemistry reaction with two steps, dependent of a hetero crosslinker (DBCO???PEG4???NHS Ester). Dynamic light scattering (DLS) and fluorimeter assays were used to evaluate the efficiency of coupling. MALDI-ToF analysis showed 3 molecules of LCPF_C1 peptide for each CR4 polymer. Moreover, microrheology showed changes on hybrids increasing the viscosity. Finally, the compounds were evaluate against four different bacteria: Staphylococcus aureus, Klebsiela pneumoneae carbapenemases (Kpc), Escherichia coli and Pseudomonas aeruginosa. It was possible to observe MIC???s against P. aeruginosa of 11 mM by using the peptide (LCPF_C1) and 55 mM for the original sequence. When the hibrids were compared to the free polymer was not found MIC values against K. pneumoneae (CR-Kp). On the other hand, the hibrids showed three times less activity than the free polymer against P. aeruginosa. No MIC values were found aganst S. aureus. Finally, against E. coli was observed a MIC value of 1000 mM for the free CR4 and 250 mM for the hibrids. On this way, the present work showed the possibility to functionalize biopolymers by using bioactive molecules coupled to biopolimers, changing the physical-chemical characteristics and increasing they applicability against bacterial infections. / Uma taxa alarmante de bact??rias tem se tornado resistente a um grande n??mero de antimicrobianos convencionais. Desta forma, a demanda por novas terapias antimicrobianas tem aumentado proporcionalmente. Assim, o uso de pept??deos antimicrobianos (PAMs) consistem em uma promissora alternativa para antibacterianos convencionais, particularmente podendo ser acoplado a estruturas moleculares para aplica????es biom??dicas, como hidrog??is para curativos e cobertura de implantes. No presente trabalho, PAMs foram quimicamente conjugados ao pol??mero hidrof??lico inspirado nas prote??nas naturais col??geno e seda CR4. O pept??deo CPF_C1 consiste em um pept??deo contendo 17 res??duos de amino??cidos isolado de Xenopus clivii, com atividade comparada ?? bact??rias Gram-negativas e -positivas. Para este estudo, a sequ??ncia original do CPF-C1 foi modificada e intitulada LCPF_C1, objetivando aumentar a dist??ncia entre a primeira glicina e a azida adicionada na por????o N-terminal. A conjuga????o entre o PAM e o pol??mero CR4 foi realizada por meio de click chemistry reaction em dois passos, dependentes do hetero crosslinker (DBCO???PEG4???NHS Ester). Ensaios de espalhamento de luz din??mico (DLS) e fluorimetria foram utilizados para avaliar a efici??ncia de acoplamento e demonstraram a presen??a do pept??deo acoplado ao pol??mero. An??lises de MALDI-ToF demonstraram 3 mol??culas do pept??deo LCPF-C1 para cada mol??cula do pol??mero CR4. Al??m disso, dados de microrreologia demonstraram mudan??as nos h??bridos como aumento de viscosidade. Finalmente, os compostos foram avaliados contra quatro bact??rias diferentes: Staphylococcus aureus, K. pneumoneae carbapenemase (Kpc), Escherichia coli e Pseudomonas aeruginosa. Foi poss??vel observar para P. aeruginosa MICs de 11 mM utilizando o pept??deo (LCPF_C1) e 55 mM para a sequ??ncia original. Quando comparados aos h??bridos em rela????o a atividade do pol??mero livre n??o foi encontrado valor de MIC contra K. pneumoneae (CR-Kp). Por outro lado, os h??bridos demonstraram um MIC cerca de tr??s vezes menor que o pol??mero livre contra P. aeruginosa. Nenhum valor de MIC foi encontrado contra S. aureus. Finalmente, contra E. coli observou-se MIC de 1000 mM para o pol??mero CR4 e 250 mM para os h??bridos. Desta forma o presente trabalho demonstrou a possibilidade de funcionalizar biopol??meros por meio do acoplamento de mol??culas bioativas, alterando suas caracter??sticas f??sico-qu??micas e aumentando sua aplicabilidade contra infec????es bacterianas.

Esta dissertação visa identificar as variáveis que possuem maior influência sobre os resultados de campanhas de publicidade digital. Para levantar possíveis variáveis que interferem na taxa de cliques (click-through rate) nos anúncios online, inicialmente foi realizada uma revisão da literatura disponível sobre o tema. Para tanto, utilizou-se como estrutura conceitual o modelo da Teoria da Informação para categorização dos fatores encontrados. A partir dessa categorização, foram selecionados fatores para um projeto de experimento fatorial utilizando análise de variância (ANOVA). Os fatores escolhidos foram a segmentação do público-alvo por gênero, o segmento econômico do anunciante e características do anúncio: cor, presença de animação e frase de chamada para ação (call to action). O experimento concluiu que a ausência de frase de chamada para ação (call to action), imagens estáticas sem animação e a aderência do público-alvo a ser atingido pela campanha ao publico do produto anunciante são as características que apresentam uma performance significativa para taxas de cliques. As conclusões do estudo apontam direcionamentos úteis para as empresas que investem em mídia digital e elaboram campanhas online de publicidade. Do ponto de vista acadêmico, a revisão da literatura e o projeto de experimento deste estudo fornecem evidências para o entendimento das principais variáveis de influência sobre este tipo de projeto. / This master thesis aims to identify factors that influence on the results of digital advertising campaigns. To understand what can increase the digital click-through rate in these campaings, the first part of this research addressed a literature review about academic and professional studies about the influencing factors of these campaigns. The identified factors were organized in three main categories from the information-processing theory: source, message and recipient dimensions. These factors were then analyzed by means of a factorial experiment project using analysis of variance (ANOVA). The factors chosen were target gender, the advertiser’s economic segment and the advertisment characteristics: color and presence of animation and call to action. The experiment concluded that some factors were meaningful for the increase of the click-through rate. The fit between advertising campaign and the advertiser’s product target, absence of call to action phrase and non-animated banners presented meaningful increases in the performances of the banners click-through rates. The conclusions of this study point useful directions for digital media advertisers. From academic point of view, the literature revision and the analysis of variance in this research provide evidences for the understanding the main influence factors in this kind of projects.

As cumarinas são estruturas interessantes aos olhos da química medicinal, apresentando diversas atividades biológicas sobre os mais variados alvos. Neste trabalho, em um primeiro momento, realizamos a extração com CO2 em meio supercrítico das cumarinas de Pterocaulon balansae, planta nativa do Rio Grande do Sul que apresenta em sua composição grandes quantidades destes compostos. A extração com CO2 supercrítico apresentou rendimentos satisfatórios em massa de sete cumarinas previamente descritas para estas espécies. Dentre estes se destacam os compostos majoritários 7-(2,3-epoxi-3-metil-3-butiloxi)-6-metoxicumarina e 5,6-dimetoxi-7-(2’,3’-epoxi-3-metilbutiloxi) cumarina. Realizamos também a síntese de 4-metilcumarinas através de reação de Pechmann, obtendo o composto LaSOM 77 (7-hidroxi-4-matilcumarina) com excelentes rendimentos, onde realizamos uma diversificação estrutural através da adição de um linker e posteriormente a síntese de triazóis através de “Click Chemistry”. Para tanto, utilizamos uma biblioteca de 35 alcinos disponíveis comercialmente e outros 3 sintetizados em nosso laboratório. Sendo assim, obtivemos uma biblioteca de 38 híbridos cumarina-triazol que apresentaram excelentes rendimentos, em tempos reacionais que variaram entre 20 e 50 minutos de reação sob irradiação de microondas. Os testes biológicos preliminares frente a linhagens cancerígenas indicaram que os compostos sintetizados apresentam potencial utilização como anticancerígenos, sendo ativos frente a linhagens celulares de câncer de pulmão, fígado e mama, apresentando baixa toxicidade em células sadias. A partir das investigações teóricas e experimentais relacionadas à este trabalho foi produzido um artigo de revisão, intitulado “New insights into the chemistry and antioxidante activity of coumarins” está aceito pelo periódico Current Topics in Medicinal Chemistry. / Coumarins are interesting structures for the medicinal chemistry, because present several biological activities. At first, we performed the supercritical CO2 extraction from Pterocaulon balansae, a plant native from Rio Grande do Sul, which has in its composition large amounts of these compounds. The extraction with supercritical CO2 showed satisfactory yields of seven coumarins previously described for this species. Among these compounds the coumarins 7-(2,3-epoxy-3-methyl-3-butyloxy)-6-methoxycoumarin e 5,6-dimethoxy-7-(2’,3’-epoxy-3-methylbutyloxy) coumarin are the majority compunds. We also performed the synthesis of 4-methylcoumarins using Pechmann reaction, obtaining the compound LaSOM 77 (7-hydroxy-4-methyl-coumarin) in excellent yield and perfomed the structural diversification trougth the addition of a linker and subsequentely synthesis of 1,2,3-triazoles by Click Chemistry. Therefore, was used a colection of 35 commercialy available alkynes and other 3 synthesized in our laboratory to obtain a colection of 38 coumarin-triazole hybrids in excellent yields and time of reaction ranging betwenn 20 and 50 minutes under microwave radiation. Preliminary biological tests against cancerous strains indicated that the synthesized compounds have potential use as anticancer agents against cell lines of lung, liver and breast cancer. From the theorical and experimental data from this work, one review paper was produced: The article is intitled “New insights into the chemistry and antioxidante activity of coumarins” is accepted to the journal "Current Topics in Medicinal Chemistry".

Submitted by Maria Aparecida (cidazen@gmail.com) on 2017-04-04T14:57:07Z No. of bitstreams: 1 Samario Jose Lima Meireles.pdf: 5051030 bytes, checksum: dda872455dd2092963a9db897ee15455 (MD5) / Made available in DSpace on 2017-04-04T14:57:07Z (GMT). No. of bitstreams: 1 Samario Jose Lima Meireles.pdf: 5051030 bytes, checksum: dda872455dd2092963a9db897ee15455 (MD5) Previous issue date: 2017-03-06 / CAPES / In this research are analyzed the processes of selection of political leaders of the maranhense branch of the Brazilian bar association, with emphasis on the period between 1983 and 2015. The investigation focused on fourteen elective disputes through which the boards of directors of the entity were chosen. In the operationalization of the study, we sought to apprehend chains of leaders-followers who competed within the institution, evidencing the flows of entries, exits, approximations and distancing. In order to do so, the trajectories of the main protagonists (egos of networks) who competed for positions of direction of the OAB/MA were reconstituted, as well as the clicks of leaders who were formed in these clashes and the cleavages constructed by means of constant realignments in the alliances. Therefore, firstly, the resources accumulated by the agents that stood out in these disputes were identified, and secondly, the networks of relations (through the use of the UCINET and NETDRAW programs) constituted and activated for electoral purposes, also seeking to reveal the social bases of interconnections, ties and links more or less ephemeral. / Nesta pesquisa são analisados os processos de seleção dos dirigentes políticos da seccional maranhense da Ordem dos Advogados do Brasil, com ênfase no período compreendido entre 1983 e 2015. A investigação centrou-se em catorze disputas eletivas mediante as quais foram escolhidas as diretorias da entidade. Na operacionalização do estudo, buscou-se apreender cadeias de líderes-seguidores que rivalizaram no âmbito da instituição, evidenciando os fluxos de entradas, saídas, aproximações e distanciamentos. Para tanto, foram reconstituídas as trajetórias dos principais protagonistas (egos de redes) que concorreram a postos de direção da OAB/MA, bem como as cliques de dirigentes que foram formadas nesses embates e as clivagens construídas por meios de realinhamentos constantes nas alianças. Sendo assim, em primeiro lugar, foram identificados os recursos acumulados pelos agentes que se destacaram nessas contendas e, em segundo lugar, as redes de relações (por intermédio do uso dos programas UCINET e NETDRAW) constituídas e ativadas com objetivos eleitorais, buscando também revelar as bases sociais de interconexões, elos e vínculos mais ou menos efêmeros.

As there is a need for fully validated drug targets in <i>Trypanosoma cruzi</i>, the genetic andbiochemical essentiality of <i>N</i>-myristoyltransferase (NMT) was assessed. The geneticrequirement was assessed using a classical gene replacement strategy, attempting tosequentially replace the endogenous alleles with drug resistance genes to generate an<i>NMT</i> null parasite. It was only possible to achieve this in the presence of an ectopiccopy of <i>NMT</i> under constitutive expression, providing the strongest evidence that thisgene is essential for the proliferation of the epimastigote. While both NMT and <i>N</i>-myristoylationwere detected in all lifecycle stages, there were subtle differences in theexpression of several myristoylated proteins. However, at least ~10 myristoylatedproteins were common throughout the lifecycle. In addition, <i>N</i>-myristoylation in thisparasite was found to be primarily associated with nascent protein synthesis, astreatment with cycloheximide reduced the number of <i>N</i>-myristoylated proteins detected. The sensitivity of epimastigotes to the inhibitor DDD85646 correlated with theexpression of NMT, suggesting it to be the target in the parasite. This was confirmedby the dose-dependent depletion of <i>N</i>-myristoylated proteins detected in parasitestreated with this compound. Mechanism of action studies revealed a cytokinesis defectcaused by the inhibition of <i>N</i>-myristoylation and NMT. Overexpression of NMT wasable to rescue these cells from this phenotype confirming that it is NMT mediated. The<i>N</i>-myristoylated proteins comprising the <i>N</i>-myristoylome of the epimastigote wereidentified using the myristic acid analog, azidomyristate and a chemical proteomicsapproach. Combining label-free and SILAC methodologies, 38 proteins were enrichedfrom azidomyristate labelled cells, 35 of which were predicted to have a glycine afterthe initial methionine. The findings from these experiments have led to the mostcomprehensive <i>N</i>-myristoylome of <i>T. cruzi</i> studied to date and provide severalhypotheses, by which the inhibition of NMT leads to the observed cytokinesis defect.

Trabalho realizado na Adclick, orientado pelo Engº Pedro Roque / Tese de mestrado integrado. Engenharia Industrial e Gestão. Faculdade de Engenharia. Universidade do Porto. 2012

Germanium nanoparticles (Ge NPs) may be fascinating for their electronic and optoelectronic properties, as the band gap of Ge NPs can be tuned from the infrared into the visible range of solar spectru. Further functionalization of those nanoparticles may potentially lead to numerous applications ranging from surface attachment, bioimaging, drug delivery and nanoparticles based devices. Blue luminescent germanium nanoparticles were synthesized from a novel top-down mechanochemical process using high energy ball milling (HEBM) of bulk germanium. Various reactive organic molecules (such as, alkynes, nitriles, azides) were used in this process to react with fresh surface and passivate the surface through Ge-C or Ge-N bond. Various purification process, such as gel permeation chromatography (GPC), Soxhlet dailysis etc. were introduced to purify nanoparticles from molecular impurities. A size separation technique was developed using GPC. The size separated Ge NPs were characterize by TEM, small angle X-ray scattering (SAXS), UV-vis absorption and photoluminescence (PL) emission spectroscopy to investigate their size selective properties. Germanium nanoparticles with alkyne termini group were prepared by HEBM of germanium with a mixture of n-alkynes and α, ω-diynes. Additional functionalization of those nanoparticles was achieved by copper(I) catalyzed azide-alkyne ""click"" reaction. A variety of organic and organometallic azides including biologically important glucals have been reacted in this manner resulting in nanopartilces adorned with ferrocenyl, trimethylsilyl, and glucal groups. Additional functionalization of those nanoparticles was achieved by reactions with various azides via a Cu(I) catalyzed azide-alkyne ""click"" reaction. Various azides, including PEG derivatives and cylcodextrin moiety, were grafted to the initially formed surface. Globular nanoparticle arrays were formed through interparticle linking via ""click"" chemistry or ""host-guest"" chemistry. Copper(I) catalyzed ""click"" chemistry also can be explored with azido-terminated Ge NPs which were synthesized by azidation of chloro-terminated Ge NPs. Water soluble PEGylated Ge NPs were synthesized by ""click"" reaction for biological application. PEGylated Ge NP clusters were prepared using α, ω-bis alkyno or bis-azido polyethylene glycol (PEG) derivatives by copper catalyzed ""click"" reaction via inter-particle linking. These nanoparticles were further functionalized by azido β-cyclodextrin (β-CD) and azido adamantane via alkyne-azide “click” reactions. Nanoparticle clusters were made from the functionalized Ge NPs by “host-guest” chemistry of β-CD functionalized Ge NPs either with adamantane functionalized Ge NPs or fullerene, C60. / acase@tulane.edu

Biomolecules are difficult to investigate in their native environment. The vast complexity of cellular systems and seldom availability of chemical reactions compatible with the physiological milieu make it a challenging task. Bioorthogonal chemical reactions serve as a key to achieve selective ligation, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionalities necessary to sustain life. In this dissertation, we focused on the synthesis of chemical reporters and probe molecules for bioorthogonal labeling through click reaction. Initially, sialic acid derivatives with a linker containing terminal alkyne functionality were synthesized. After the synthesis of azide derivatives of fluorescent dyes as counter partners, they were conjugated with sialic acids through Cu(I) catalyzed alkyne azide cycloaddition (CuAAC). The successful in vitro conjugation of Sia and fluorescent dyes was followed by metabolic tagging of human larynx carcinoma (HEp-2) and the carcinoma of Chinese hamster ovary (CHO­K1) with alkynated Sia that were subsequently ligated with fluorescein azide. Finally, the stained cells were subjected to fluorescent microscopy to obtain their images. To enable the click reaction compatible to in vivo applications, the reactivity of cyclooctyne was enhanced by two different approaches. In a first approach, following the Bertozzi’s strategy, two fluorine atoms were introduced adjacent to the alkyne to lower the LUMO. In a second strategy the ring strain of cyclooctyne was attempted to be enhanced by the introduction of an amide group. In addition, glutarimide derivatives with free amino and carboxylic acid functional groups were synthesized by domino-Michael addition-cyclization-reaction. / Biomoleküle sind schwer in ihrer natürlichen Umgebung zu untersuchen. Die enorme Komplexizität zellulärer Systeme und die geringe Verfügbarkeit von chemischen Reaktionen, welche mit physiologischen Bedingungen kompatibel sind, stellen eine große Herausforderung dar. Bioorthogonale Reaktionen dienen hierbei als Schlüssel für eine selektive Ligation, bei der die Komponenten schnell, selektiv und unter genannten Bedingungen miteinander reagieren. Der Fokus dieser Dissertation lag auf der Synthese von chemischen Reportermolekülen, welche für bioorthogonale Markierungsversuche mithilfe einer Klick-Reaktion eingesetzt werden können. Dafür wurden zunächst Derivate der Sialinsäure mit einem Linker, der eine endständige Alkinfunktion trägt, synthetisiert und diese mit ebenfalls in dieser Arbeit dargestellten Azidofluoreszenzfarbstoffen in einer Cu(I)-katalysierten Alkin-Azid-Cycloaddition (CuAAC) konjugiert. Nach erfolgreicher in vitro Durchführung wurden Zellen des menschlichen Larynx Karzinoms (HEp-2) und Zellen des Ovariumkarzinoms des chinesischen Hamsters metabolisch mit alkinfunktionalisierten Sialinsäuren markiert und anschließend mit Fluoresceinazid ligiert. Fluoreszenzmikroskopie an diesen Zellen demonstrierte den erfolgreichen Einbau der Sialinderivate. Um die Klickreaktion verträglicher für in vivo Anwendungen zu gestalten, wurde versucht die Reaktivität des Cyclooctin durch zwei verschiedene Herangehensweisen zu erhöhen. Zum einen wurden nach Strategie von Bertozzi zwei Fluoratome benachbart zur Alkingruppe eingeführt, um die LUMO-Energie zu erniedrigen. Zum anderen wurde versucht die Ringspannung des Cyclooctin durch Einführung einer Amidgruppe zu erhöhen. Neben dem Klickprojekt wurden in dieser Arbeit außerdem Glutarimidderivate mit freien Amino- und Carbonsäuregruppen über eine Domino-Michael-Additions-Zyklisierungsreaktion dargestellt.