No description available.

Marburg, Universiẗat, Diss. : 1994.

We demonstrate a novel and ready to prepare thermoreversible hetero Diels–Alder dilinker on the basis of dithiooxalates, enabling the mild, rapid and catalyst-free linkage of diverse diene species under ambient conditions for applications in the fields of, for example, modular ligation, self-healing or recyclable materials and surface modification amongst others. The linker was studied using quantum chemical calculations, and experimentally in small molecular reactions via UV/Vis spectroscopy, mass spectrometry and NMR as well as in step-growth polymerizations with diene-difunctional building blocks – characterized via (temperature dependent) SEC and HT NMR – as an example for efficient polymer ligation.

Asymmetric catalysis is one of the most effective ways to control a target molecule’s stereochemistry. Through the development of a wide variety of chiral transition metal complexes, synthetic chemists are given the tools they need to synthesize the desired enantiomer of numerous compounds. This work focuses on exploiting the non-innocent ligand reactivity of metal bis-dithiolenes with multiple conjugated π systems in order to synthesize chiral ligands. Recent work has shown that platinum bis-dithiolene reacts with dienes stereoselectively to form a racemic mix of C2 -chiral thioether ligands. The present contribution will show approaches to synthesizing chiral dienes and organometallic complexes with potential applications for asymmetric allylic substitution reactions. Dienes with various chiral auxiliaries were reacted with platinum dithiolene and monitored through NMR spectroscopy. Attempts to synthesis palladium bis-dithiolene complexes, not previously seen in the literature were made, and the reaction of α-β unsaturated ketones with metal bis-dithiolenes was explored.

Asymmetric catalysis is one of the most effective ways to control a target molecule’s stereochemistry. Through the development of a wide variety of chiral transition metal complexes, synthetic chemists are given the tools they need to synthesize the desired enantiomer of numerous compounds. This work focuses on exploiting the non-innocent ligand reactivity of metal bis-dithiolenes with multiple conjugated π systems in order to synthesize chiral ligands. Recent work has shown that platinum bis-dithiolene reacts with dienes stereoselectively to form a racemic mix of C2 -chiral thioether ligands. The present contribution will show approaches to synthesizing chiral dienes and organometallic complexes with potential applications for asymmetric allylic substitution reactions. Dienes with various chiral auxiliaries were reacted with platinum dithiolene and monitored through NMR spectroscopy. Attempts to synthesis palladium bis-dithiolene complexes, not previously seen in the literature were made, and the reaction of α-β unsaturated ketones with metal bis-dithiolenes was explored.

This thesis describes the efforts towards the synthesis of the guaiane-6,12-olide skeleton, which characterises the guaianolide family of bioactive natural compounds. Two approaches have been investigated: the intramolecular hetero Diels Alder (IMHDA) reaction and the intramolecular carbonyl ene reaction. This thesis has been divided in three sections: the first part gives a general background about the guaianolides, the second section describes the synthetic approaches we investigated and, finally, the third section reports the experimental details. The first section gives a brief overview about the biosynthesis, the biological activities of the guaianolides, and the most interesting synthetic approaches to obtain them. The second section describes the two different approaches we investigated and gives a theoretical background about the main chemical transformations used. At first, the IMHDA reaction approach is described: a brief overview of palladium catalysis and Diels Alder reaction is given, and it is followed by the results and discussion of our study. Similarly, a theoretical background of the Alder ene reaction is given, before the results and discussion of the intramolecular carbonyl ene reaction approach are described: particular importance is given to the reasoning that led to the assignment of the relative configuration of the cycloadducts obtained, and to the rationalisation of this stereochemical outcome. Finally, the third section gives a complete description of the experimental procedures followed, and of the experimental data for the synthetic studies performed in the previous chapter.

The tree and shrub species belonging to the Myrtaceae family are rich in structurally diverse meroterpenoids which possess anti-cancer, anti-malarial, anti-bacterial, anti-viral, and anti-inflammatory biological activities. Many of the natural products belonging to this family are derived from two common precursors: syncarpic acid and formyl phloroglucinol. The dissertation research described herein is focused on the total synthesis of two subclasses of natural products: syncarpic acid-derived meroterpenoids and formyl phloroglucinol meroterpenoids. The synthetic methodologies disclosed were developed to enrich the chemodiversity of these novel meroterpenoids by providing efficient access to such scaffolds and derivatives. Rhodomyrtusials A–C, the first examples of syncarpic acid-derived sesquiterpene meroterpenoids featuring a unique 6/5/5/9/4 fused pentacyclic ring system, were isolated from Rhodomyrtus tomentosa along with several biogenetically-related dihydropyran isomers. Two bis-furans and one dihydropyran isomer showed acetylcholinesterase (AChE) inhibitory activity. Herein, the bioinspired total syntheses of six isolates were achieved in six steps utilizing a reactive enetrione intermediate generated in situ from a readily available hydroxy-endoperoxide precursor are reported. Further evaluation of alkene reaction partners identified additional modes of reactivity for the enetrione, leading to the production of novel small molecule scaffolds. Furthermore, computational studies have identified a valid asynchronous, concerted pathway leading to the formation of the bis-furan containing natural products. Eucalyptusdimers A−C, three dimeric phellandrene-derived formyl phloroglucinol meroterpenoids featuring an unprecedented, fused skeleton between two phellandrene and two acylphloroglucinol subunits, along with one biogenetically related intermediate eucalyprobusone A, were isolated from the fruits of Eucalyptus robusta. These isolates also showed AChE inhibitory activity. A one-pot, three-component reaction was identified to achieve the synthesis of eucalyprobusone A and subsequent synthetic efforts towards eucalyptusdimers A and B via hetero-Diels Alder (HDA) [4+2] cycloaddition with known terpene, alpha-phellandrene are outlined. Initial efforts failed to promote the desired HDA cycloaddition, which led to alternate exploration of oxidative [4+2] cycloaddition chemistry. Using this revised strategy, the synthesis of several Eucalyptus metabolites including grandinol, euglobal IIc, and euglobal T1 was achieved. Future efforts and synthetic strategies to afford the eucalyptusdimers from these precursors are provided. / 2025-09-20T00:00:00Z

No description available.

Le paludisme et la schistosomiase sont des maladies parasitaires tropicales qui affectent plus de 800 millions de personnes dans le monde, notamment dans des pays en voie de développement. Bien qu’il existe des traitements contre ces infections, de nombreuses résistances à ces dernières sont apparues les dernières décennies. Malgré « l’urgence humanitaire », l’industrie pharmaceutique n’est que très peu investie dans la conception et le développement de nouvelles thérapies pour ces maladies dites « de la pauvreté ». Afin de trouver des nouveaux candidat-médicaments contre ces parasites, une librairie de 3- benzyl-2-méthylnaphtoquinones portant différents substituants sur la partie benzylique avait été précédemment développée au sein du laboratoire d’accueil. Malgré la puissante activité antipaludique d’une molécule identifiée comme tête de série, il n’y avait pas de guérison totale des souris infectées, suggérant que les naphtoquinones sont rapidement métabolisées en milieu biologique. Une plateforme de synthèse a été établie permettant d’obtenir de façon relativement simple des nouvelles naphtoquinones avec des substituants divers sur la partie aromatique, et ainsi, améliorer leurs propriétés pharmacocinétiques, d’une part en augmentant leur demie-vie, leur solubilité, et leur biodisponibilité dans les milieux biologiques, d’autre part en modifiant leurs potentiels redox, et en étudiant les métabolites actifs. L’ensemble de ce travail nous a permis de synthétiser une cinquantaine de nouvelles naphtoquinones et ainsi d’obtenir les premières connaissances des relations structure/activité, qui serviront en infochimie à développer des outils de prédiction pour la chimie médicinale redox. / Malaria and schistosomiasis are tropical parasitic diseases, which affect more than 800 million people worldwide, especially in developing countries. Multidrug-resistance of malarial strains toward broadly used antimalarial drug treatment (e.g. chloroquine, quinine) has spread all over the world in the last five decades. Despite the humanitarian emergency, pharmaceutical industries are not investing in the research and production of new therapies for diseases of poverty.In order to develop new potential ethical drugs against these parasites, a library of polysubstituted 3-benzyl-2-methylnaphthoquine derivatives functionalized at the benzylic core were previously synthetized in the host laboratory. Despite the strong antimalarial activity of an identified lead compound, the infected mice were not totally cured, suggesting that the naphthoquinones are rapidly metabolized under biological conditions.A platform of synthetic methodologies has been established in order to produce, via straightforward routes, new polysubstituted benzylmenadione derivatives functionalized at the aromatic ring of the naphthoquinone core, and to improve their pharmacokinetic properties by (i) increasing their half-life, solubility, bioavailability, (ii) modifying their redox potentials, and (iii) studying their active metabolites. The synthetic methodologies exemplified with 50 described compounds provide the structure–activity relationships as the basis for the development of new cheminformatics tools to be used in redox medicinal chemistry .

Asymmetric synthesis and catalysis is one of the leading research areas in chemistry society, for its versatility and efficiency in obtaining chiral molecules that found the vast majority in natural active compounds and synthetic drugs. Developing asymmetric catalytic methodology is at the frontier in both industrial and academic research laboratories. Enantioselective organocatalysis has emerged as a powerful synthetic tool that is complementary to metal-catalyzed transformations. The development of chiral phosphoric acid and metal phosphate as catalysts has been a breakthrough in recent years. Chiral phosphoric acids have been shown to be powerful catalysts in many organic transformations. Moreover, chiral metal phosphates, which formed by simply replacing the proton in phosphoric acid with metals, have introduced new catalytic activations and broaden the scope of phosphoric acids. This thesis details new highly enantioselective chiral phosphoric acid-catalyzed Pinacol rearrangement and robust alkaline phosphates catalytic system, which utilizes novel carbonyl activation. The Pinacol rearrangement has long been known to be difficult to control in terms of regioselectivity and stereoselectivity. The initial studies found that indolyl-diol compounds can be treated with chiral phosphoric acids to afford the Pinacol rearrangement with high regio- and enantioselectivity. Over 16 chiral phosphoric acids were screened, and it was found an H8-BINOL-phosphoric acid variant with 1-naphthyl groups at 3 and 3' position was the excellent catalyst. This asymmetric transformation is tolerant toward variety of substituents both on the indole ring and migrating groups. During the study, it was found that different ways to generate the catalyst had critical effect on this catalytic transformation. Only those phosphoric acids washed with HCl after column chromatography afforded the rearrangement products with high enantioselectivity. And those without treating with HCl were found contaminated by alkaline metals. These "contamination" catalysts were also found active with carbonyl activations. A highly enantioselective catalytic hetero-Diels-Alder reaction of alpha-keto esters has been developed with chiral alkaline metal phosphates. A calcium 1-naphthyl-BINOL phosphate was found to be the optimum catalyst. A large range of alpha-keto esters as well as isatins can be applied in this alkaline phosphates catalytic system with high efficiency and selectivity. The structure of the catalyst is detailed for the first time by X-ray crystal structure analysis. A proposed Transition state model is provided based on the catalyst crystal structure and Raman spectroscopy analysis. This methodology was further developed with an asymmetric Mukaiyama-Michael addition of beta,gamma-unsaturated alpha-keto ester. The best catalyst was found to be a magnesium chiral phosphate. And the transformation was found capable of tolerating a wide variety of beta,gamma-unsaturated alpha-keto esters.