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Isatin-derived 1,2,4-triazines were employed as electron deficient azadienes in inverse electron demand Diels-Alder (IEDDA) chemistry with tethered alkynyl dienophiles, leading to biologically interesting heterocyclic lactam- and lactone-annulated α-carbolines in excellent yields under microwave promotion. The chemistry scope was probed using various alkynyl amines and alcohols, and the impact of the tether length between the triazines and the dienophiles was also investigated. This IEDDA methodology was subsequently applied to the synthesis of an α-carboline library, producing eighty-eight members starting with various isatin-derived triazines, indole-derivatives, and propargylamine derivatives. In a related project, a regioselective Lewis acid catalyzed amidation of dimethyl 5H-pyridazino[4,5-b]indole-1,4-dicarboxylate was established to selectively direct the amidation to occur at either the C1 or C4 ester positions. This chemistry was then applied to tether dienophiles to the pyridazinoindole ring via an amide linkage. Subsequent IEDDA cycloadditions of these pyridazinoindole/dienophile pairs afforded carbazoles in excellent yields under thermal conditions. The scope of this chemistry scope was also thoroughly probed, leading to a library of one hundred and eighty-eight members. The synthesis of a third heterocyclic scaffold using Diels-Alder chemistry was also accomplished. Asymmetric cycloadditions of anthrone with various maleimides were successfully achieved using different chiral organocatalysts. The identity of the optimal catalytic system depended upon the dienophile, with good enantioselectivities achieved (78-83% ee). This chemistry was successfully applied as the stereocontrol element in a Diels-Alder/Functional Group Transformation/retro-Diels-Alder sequence to prepare alkaloidal scaffolds in an optically enriched form.

L’étude de plantes utilisées en médecine traditionnelle camerounaise contre le paludisme a révélé des activités antiprotozoaires pour des espèces du genre Psorospermum conduisant à l’isolement d’anthranoïdes prénylés. De nouveaux fractionnements basés sur des techniques chromatographiques en polarité de phase inverse et de partage centrifuge ont permis d’isoler 9 vismiones de l’écorce de P. glaberrimum qui ont montré de fortes activités antileishmaniennes (30 nM < CI50 < 827 nM). Un protocole d’isolement à l’échelle du gramme de ces molécules, sensibles aux conditions classiques de purification, a été développé pour fournir les quantités nécessaires à une démarche d’hémisynthèse et pour comprendre leur mécanisme d’action. La répartition de ces molécules dans les organes de 10 espèces de Psorospermum a été étudiée. Une approche de synthèse organique a également été développée afin d’obtenir des analogues, déterminer leurs activités antiprotozoaires et leurs relations de structure-activité. / The screening of plants used in Cameroonian traditional medicine against malaria revealed significant antiprotozoal activities for species belonging to the Psorospermum genus and led to the isolation of prenylated anthranoids. Further fractionations based on reversed-phase and centrifugal partition chromatography allowed us to isolate 9 vismiones from the bark of P. glaberrimum. All these compounds exhibited strong antileishmanial activities (30 nM<IC50<827 nM).A gram-scale isolation protocol of these highly unstable compounds, when traditional ill-suited purification processes are used, has been developed to provide enough starting material for further hemisynthesis steps and to investigate their mechanism of action. The repartition of these metabolites in different parts of 10 Psorospermum species has been studied. A synthetic approach has also been developed to obtain anthranoid analogues to investigate their antiprotozoal activities and explore structure-activity relationships.