En aquesta tesi doctoral es va estudiar la preparació de pèptids biarílics en fase sòlida. En primer lloc, es varen borilar residus de fenilalanina o tirosina presents a la seqüència peptídica a través d’una reacció de Miyaura. A continuació, es varen arilar els boronats resultants a través d’una reacció de Suzuki-Miyaura sota irradiació de microones, utilitzant diversos halurs d’aril i haloaminoàcids. La metodologia trobada es va estendre a la preparació de pèptids biarílics cíclics. Aquesta aproximació presenta l’avantatge d’evitar la síntesi en dissolució i la purificació del boronoaminoàcid. A més, permet la preparació d’una àmplia diversitat de pèptids biarílics a partir d’un únic boronopèptid. L’avaluació de l’activitat biològica dels pèptids sintetitzats va permetre idenficar seqüències actives enfront dels bacteris Erwinia amylovora, Xanthomonas vesicatoria, i Pseudomonas syringae, que són responsables de malalties greus en plantes d’interès econòmic com pereres i pomeres, i que varen resultar ser molt poc tòxics enfront cèl•lules eucariotes. / The present PhD study was focused on the preparation of biaryl peptides on solid-phase. First, phenylalanine or tyrosine residues were borylated through a Miyaura reaction. Then, the resulting boronates were arylated via a Suzuki-Miyaura reaction under microwave irradiation, using a range of aryl halides and haloamino acids. This methodology was extended to the solid-phase synthesis of biaryl cyclic peptides. This strategy is advantageous because it avoids the synthesis and purification of amino acid boronates in solution. Moreover, it allows the preparation of a large diversity of biaryl peptides from a single boronopeptide intermediate. The evaluation of the biological activity allowed the identification of active sequences against the economically important plant pathogenic bacteria Erwinia amylovora, Xanthomonas vesicatoria, and Pseudomonas syringae, and moreover they were not toxic against eukaryotic cells.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Nesta monografia foram desenvolvidas metodologias sintéticas para a funcionalização das 2-(S)-isopropil-5-iodo-pirimidinonas, utilizando a reação de acoplamento cruzado de Suzuki-Miyaura e a reação de cicloadição azida-acetileno com cobre, através de estratégias simples e eficientes que permitiram a preparação de uma série de compostos com grande diversidade estrutural. Inicialmente descreve-se a síntese da 2-(S)-isopropil-5-iodo-pirimidinona (S)- 3, a partir da (S)-asparagina enantiomericamente pura 1, um aminoácido barato e de fácil acesso, produzindo na primeira etapa o 2-(S)-isopropil-peridropirimidinona-6- ácido carboxílico (2S,6S)-2, que reagindo com diacetoxiiodo benzeno/iodo e BF3.OEt2, gera a pirimidinona (S)-3. Em seguida, preparou-se uma série de 2-(S)-isopropil-5-aril-pirimidinonas (S)- 6a-q e 2-(S)-isopropil-5-alquinil-pirimidinonas (S)-7a-q, através da reação de acoplamento cruzado de Suzuki-Miyaura, sob catálise de paládio, utilizando aril- (4aq) e alquiniltrifluoroboratos de potássio (5a-q), respectivamente. Desta forma sintetizou-se uma variedade de pirimidinonas com alterações programadas de substituintes na posição 5 do anel, com rendimentos de 15% a 95%. Ainda a fim de obter algumas pirimidinonas com substituintes acetilênicos alquílicos 9a-f, utilizou-se a metodologia de acoplamento de Sonogashira. Em todos os casos obtiveram-se bons rendimentos. Dando sequência ao projeto, sintetizou-se as 2-(S)-isopropil-pirimidinonas funcionalizadas na posição C5 com anéis triazólicos substituídos na posição N1 (S)- 11a-k, através da reação de cicloadição azida-acetileno utilizando CuI como fonte de cobre e ondas ultra-sônicas como fonte de energia. Preparou-se diversos compostos, todos com rendimentos variando de 79% a 87% em 5 minutos de reação. Por último, através da redução da dupla ligação endocíclica dos compostos (S)-6a, 6b, 6g, 6l e 6n e posterior hidrólise utilizando radiação microondas proporcionou a obtenção de α-aril β-aminoácidos altamente enantioenriquecidos. / This monograph shows the development of a synthetic methodology for the functionalization of 2-(S)-isopropyl-5-iodo-pyrimidinones using either Suzuki-Miyaura cross-coupling reactions or cycloaddition reactions of azide-acetylenes with copper, through a simple and efficient pathway enabling the preparation of a series of structurally diverse compounds. This paper begins by describing the synthesis of 2-(S)-isopropyl-5-iodopyrimidinones (S)-3, from enantiomerically pure (S)-asparagine 1. This inexpensive and readily available amino acid forms 2-(S)-isopropyl-perhidropyrimidinone-6- carboxylic acid (2S, 6S)-2, which is reacted with DIB / iodine and BF3·OEt2 to form pyrimidinone (S)-3. Using palladium-catalyzed Suzuki-Miyaura cross-coupling reactions, a series of 2-(S)-isopropyl-5-arylpyrimidinones (S)-6a-q and 2-(S)-isopropyl-5- alkynylpyrimidinones (S)-7a-q were prepared using potassium aryl- (4a-q) and alkynyltrifluoroborates (5a-q), respectively. With this reaction, a variety of pyrimidinones with different substituents at position 5 of the ring were synthesized, with yields ranging from 15% to 95%. The Sonogashira coupling reaction was used to prepare pyrimidinones with alkyl acetylenic substituents (S)-9a-f, giving good yields in all cases. 2-(S)-Isopropylpyrimidinones were then functionalized in the C5 position with N1 (S)-11a-k substituted triazole rings. These functionalizations were performed by the cycloaddition of azide-acetylenes using CuI and ultrasonic waves, which provided enough energy to reduce the reaction time to only five minutes. Several different variations of this compound were prepared, all with yields between 78% and 87%. Finally, the endocyclic double bonds in compounds (S)-6a, 6b, 6g, 6l and 6n were reduced, followed by a hydrolysis using microwave radiation to afford the highly enantioenriched α-aryl β-amino acids.

Neste trabalho foi desenvolvido uma metodologia sintética para a obtenção de adutos de Knoevenagel empregando a radiação de micro-ondas. Os adutos foram usados como precursores sintéticos para a obtenção de compostos tetrazólicos, reações de acoplamento de Suzuki-Miyaura, adutos cromenos e em bio-hidrogenação. A primeira etapa realizada foi a reação e a otimização da condensação de Knoevenagel usando derivados de aldeído aromático, malononitrila e água em um reator de micro-ondas por 30 min, 20 W fornecendo rendimentos de 80-99 %. Também foi observado que para o trans-metil-cinamaldeído ocorreu a formação do produto de condensação de Knoevenagel e posteriormente a formação de um produto dimérico com rendimento de 96 % por uma reação de ciclo adição [2+2] via fotoquímica. Adicionalmente foi realizada a síntese de adutos de Knoevenagel com aldeídos aromáticos e cianoacetamida fornecendo produtos diaestereoisoméricos com configuração E e rendimentos entre 90-99 %. Na segunda etapa foi realizada a obtenção de compostos tetrazólicos via one-pot entre aldeídos aromáticos, malononitrila e azida de sódio empregando água como solvente em um reator de micro-ondas por 4 h, 60 W fornecendo rendimentos de 85-99 %. Foi realizado o uso de aditivos de caráter ácido-básico na síntese do tetrazóis, observando que para o sistema N(Et)3-CuSO4 forneceu um rendimento de 90 % em um tempo de 2 h para (E)-3-fenil-2-(1H-tetrazol-5-il)acrilonitrila. Na terceira parte foram desenvolvidas reações de acoplamento de Suzuki-Miyaura a partir dos adutos de Knoevenagel com grupos halogênios (F, Cl e Br) em um reator de micro-ondas por 30 min, 60W fornecendo rendimentos de 80-97 %. Também foi realizada a reação de Knoevenagel-Suzuki-Miyaura one-pot empregando a radiação de micro-ondas fornecendo rendimentos de 82-98 %. Na quarta parte do trabalho foram sintetizados cromenos a partir de adutos de Knoevenagel com 5,5-dimetil-1,3-ciclo-hexanodiona em um reator de micro-ondas por 25 min, 60 W fornecendo rendimentos de 94-99 %. Também foram obtidos cromenos com os compostos tetrazólicos derivados de adutos de Knoevenagel por radiação micro-ondas fornecendo rendimentos de 85-98 %. Por último os adutos de Knoevenagel foram bio-hidrogenados pelo fungo marinho Penicillum citrinum CBMAI 1186 obtendo rendimentos de reação entre 12-99 %. Observou-se para a 2-(4-nitrobenzilideno)malononitrila uma reação de retro-Knoevenagel causada por efeitos eletrônicos eletroatratores. Também observou-se a presença de várias enzimas no meio de cultura de fungo P. citrinum CBMAI 1186 como: enoato redutase, nitro redutase, ceto redutase e nitrila hidratase. Também realizaram-se estudos dos tempos de reação da síntese de Knoevenagel por micro-ondas, para o qual foram empregados aditivos como: SiO4, CuSO4, imidazol, fibroína, fibra da paina e fibroína-CuSO4. Este último aditivo forneceu um rendimento de 74 % em 10 min para a 2-benzilidenomalononitrila. Em geral o estudo desenvolvido na otimização da reação de condensação de Knoevenagel e o desenvolvimento da metodologia para a obtenção de compostos tetrazólicos, adutos de acoplamento de Suzuki-Miyaura, cromenos foram bastante satisfatórios, assim como, as reações de bio-hidrogenação de sistemas α,β-insaturados. / The present work describes a synthetic methodology to obtain Knoevenagel adducts by microwave radiation. The adducts were used as synthetic precursors to obtain tetrazole compounds, Suzuki-Miyaura coupling reactions, chromene adducts and biohydrogenation. The first step was the reaction and optimization of Knoevenagel condensation using aromatic derivatives aldehyde, malononitrile and water in a microwave reactor for 30 min to obtain 80-99 % yield. Was observed that for trans-methyl cinnamaldehyde the Knoevenagel condensation product and subsequently the dimeric product with 96 % yield by [2 + 2] cycloaddition reaction photochemistry. Additionally, the synthesis of Knoevenagel adducts with aromatic aldehydes and cyanoacetamide was performed providing diastereoisomeric products with E-configuration in 90-99% yield. In the second step, tetrazole compounds were obtained via one-pot reactions between aromatic aldehydes, malononitrile and sodium azide using water as the solvent in a microwave reactor for 4 h, 60 W to obtain 85-99% yields. The use acid-base additives in the synthesis of (E)-3-phenyl-2-(1H-tetrazol-5-yl)acrylonitrile was develoment with N(Et)3-CuSO4 system, to give 90 % yields in 2 h, 60 W. In the third part, Suzuki-Miyaura coupling reactions were developed from the Knoevenagel adducts with halogen groups (F, Cl and Br) in a microwave reactor for 30 min, 60W providing yields of 80-97 %. The Knoevenagel-Suzuki-Miyaura one-pot reaction was also employed by employing microwave radiation with yields of 82-98 %. In the fourth part of this work, chromene products were synthesized from Knoevenagel adducts with 5,5-dimethyl-1,3-cyclohexanedione in a microwave reactor for 25 min, 60 W with yields 94-99 %. Chromenes adducts were also obtained with the tetrazole compounds by microwave radiation with yields of 85-98%. Finally, the Knoevenagel adducts were biohydrogenated by the marine fungi Penicillum citrinum CBMAI 1186 and was obtained 12-99 % yields. The reaction of retro-Knoevenagel was observed to 2-(4-nitrobenzylidene)malononitrile cause by highly electro-electronic electronic effects. The presence of several enzymes in the fungi culture medium P. citrinum CBMAI 1186 was also observed as enoate reductase, nitro reductase, keto reductase and nitrile hydratase. Other studies were carried out to improve the Knoevenagel synthesis by microwave using additives such as SiO4, CuSO4, imidazole, fibroin and fibroin-CuSO4. For fibroin-CuSO4 the yield was 74% in 10 min to 2-benzylidenemalononitrile. In general, the optimization of the Knoevenagel condensation reaction and the development of the synthetic methodology to obtain tetrazole compounds, Suzuku-Miyaura coupling adducts, chromene adducts was very satisfactory as well as the biohydrogenation reactions of α,β systems unsaturated.

Une série de calixarènes portant une unité imidazolium ou deux, en conformation cône ont été synthétisés et caractérisés par différentes méthodes. Ces sels chargés positivement constituaient des précurseurs de carbènes N-hétérocycliques pour la synthèse de complexes de nickel correspondants. Les complexes Ni-NHC-calix[4]arènes obtenus ont été testés dans la catalyse de la réaction de couplage croisé de Suzuki-Miyaura. Des moyennes à bonnes conversions ont été obtenues selon l’espacement du centre métallique de la cavité calixarénique, ainsi que le nombre de centre métallique présents sur la même plateforme. / A series of new calix[4]arenes bearing one or two imidazoliums units in the lower rim were synthesized as precursors of N-heterocyclic carbenes for the synthesis of the corresponding nickel complexes. All products obtained were characterized by NMR spectroscopy, microanalysis and mass spectroscopy and was revealed to be in cone conformation. The application of Ni-NHC-calix[4]arene in Suzuki-Miyaura cross coupling showed moderate to good conversions. This is been depending on the length of the alkyl chain and the number of the catalytic centers grafted on the platform.

Neste trabalho foi desenvolvido uma metodologia sintética para a obtenção de adutos de Knoevenagel empregando a radiação de micro-ondas. Os adutos foram usados como precursores sintéticos para a obtenção de compostos tetrazólicos, reações de acoplamento de Suzuki-Miyaura, adutos cromenos e em bio-hidrogenação. A primeira etapa realizada foi a reação e a otimização da condensação de Knoevenagel usando derivados de aldeído aromático, malononitrila e água em um reator de micro-ondas por 30 min, 20 W fornecendo rendimentos de 80-99 %. Também foi observado que para o trans-metil-cinamaldeído ocorreu a formação do produto de condensação de Knoevenagel e posteriormente a formação de um produto dimérico com rendimento de 96 % por uma reação de ciclo adição [2+2] via fotoquímica. Adicionalmente foi realizada a síntese de adutos de Knoevenagel com aldeídos aromáticos e cianoacetamida fornecendo produtos diaestereoisoméricos com configuração E e rendimentos entre 90-99 %. Na segunda etapa foi realizada a obtenção de compostos tetrazólicos via one-pot entre aldeídos aromáticos, malononitrila e azida de sódio empregando água como solvente em um reator de micro-ondas por 4 h, 60 W fornecendo rendimentos de 85-99 %. Foi realizado o uso de aditivos de caráter ácido-básico na síntese do tetrazóis, observando que para o sistema N(Et)3-CuSO4 forneceu um rendimento de 90 % em um tempo de 2 h para (E)-3-fenil-2-(1H-tetrazol-5-il)acrilonitrila. Na terceira parte foram desenvolvidas reações de acoplamento de Suzuki-Miyaura a partir dos adutos de Knoevenagel com grupos halogênios (F, Cl e Br) em um reator de micro-ondas por 30 min, 60W fornecendo rendimentos de 80-97 %. Também foi realizada a reação de Knoevenagel-Suzuki-Miyaura one-pot empregando a radiação de micro-ondas fornecendo rendimentos de 82-98 %. Na quarta parte do trabalho foram sintetizados cromenos a partir de adutos de Knoevenagel com 5,5-dimetil-1,3-ciclo-hexanodiona em um reator de micro-ondas por 25 min, 60 W fornecendo rendimentos de 94-99 %. Também foram obtidos cromenos com os compostos tetrazólicos derivados de adutos de Knoevenagel por radiação micro-ondas fornecendo rendimentos de 85-98 %. Por último os adutos de Knoevenagel foram bio-hidrogenados pelo fungo marinho Penicillum citrinum CBMAI 1186 obtendo rendimentos de reação entre 12-99 %. Observou-se para a 2-(4-nitrobenzilideno)malononitrila uma reação de retro-Knoevenagel causada por efeitos eletrônicos eletroatratores. Também observou-se a presença de várias enzimas no meio de cultura de fungo P. citrinum CBMAI 1186 como: enoato redutase, nitro redutase, ceto redutase e nitrila hidratase. Também realizaram-se estudos dos tempos de reação da síntese de Knoevenagel por micro-ondas, para o qual foram empregados aditivos como: SiO4, CuSO4, imidazol, fibroína, fibra da paina e fibroína-CuSO4. Este último aditivo forneceu um rendimento de 74 % em 10 min para a 2-benzilidenomalononitrila. Em geral o estudo desenvolvido na otimização da reação de condensação de Knoevenagel e o desenvolvimento da metodologia para a obtenção de compostos tetrazólicos, adutos de acoplamento de Suzuki-Miyaura, cromenos foram bastante satisfatórios, assim como, as reações de bio-hidrogenação de sistemas α,β-insaturados. / The present work describes a synthetic methodology to obtain Knoevenagel adducts by microwave radiation. The adducts were used as synthetic precursors to obtain tetrazole compounds, Suzuki-Miyaura coupling reactions, chromene adducts and biohydrogenation. The first step was the reaction and optimization of Knoevenagel condensation using aromatic derivatives aldehyde, malononitrile and water in a microwave reactor for 30 min to obtain 80-99 % yield. Was observed that for trans-methyl cinnamaldehyde the Knoevenagel condensation product and subsequently the dimeric product with 96 % yield by [2 + 2] cycloaddition reaction photochemistry. Additionally, the synthesis of Knoevenagel adducts with aromatic aldehydes and cyanoacetamide was performed providing diastereoisomeric products with E-configuration in 90-99% yield. In the second step, tetrazole compounds were obtained via one-pot reactions between aromatic aldehydes, malononitrile and sodium azide using water as the solvent in a microwave reactor for 4 h, 60 W to obtain 85-99% yields. The use acid-base additives in the synthesis of (E)-3-phenyl-2-(1H-tetrazol-5-yl)acrylonitrile was develoment with N(Et)3-CuSO4 system, to give 90 % yields in 2 h, 60 W. In the third part, Suzuki-Miyaura coupling reactions were developed from the Knoevenagel adducts with halogen groups (F, Cl and Br) in a microwave reactor for 30 min, 60W providing yields of 80-97 %. The Knoevenagel-Suzuki-Miyaura one-pot reaction was also employed by employing microwave radiation with yields of 82-98 %. In the fourth part of this work, chromene products were synthesized from Knoevenagel adducts with 5,5-dimethyl-1,3-cyclohexanedione in a microwave reactor for 25 min, 60 W with yields 94-99 %. Chromenes adducts were also obtained with the tetrazole compounds by microwave radiation with yields of 85-98%. Finally, the Knoevenagel adducts were biohydrogenated by the marine fungi Penicillum citrinum CBMAI 1186 and was obtained 12-99 % yields. The reaction of retro-Knoevenagel was observed to 2-(4-nitrobenzylidene)malononitrile cause by highly electro-electronic electronic effects. The presence of several enzymes in the fungi culture medium P. citrinum CBMAI 1186 was also observed as enoate reductase, nitro reductase, keto reductase and nitrile hydratase. Other studies were carried out to improve the Knoevenagel synthesis by microwave using additives such as SiO4, CuSO4, imidazole, fibroin and fibroin-CuSO4. For fibroin-CuSO4 the yield was 74% in 10 min to 2-benzylidenemalononitrile. In general, the optimization of the Knoevenagel condensation reaction and the development of the synthetic methodology to obtain tetrazole compounds, Suzuku-Miyaura coupling adducts, chromene adducts was very satisfactory as well as the biohydrogenation reactions of α,β systems unsaturated.

Le N-acétylcolchinol est un composé hémi-synthétique connu pour inhiber la polymérisation de la tubuline en microtubules. Il a montré une activité prometteuse en tant qu’agent ciblant la vascularisation tumorale, cependant, sa cardiotoxicité a conduit à l’arrêt des essais cliniques en phase I. Cette thèse porte sur la synthèse et l'évaluation biologique de nouveaux allocolchicinoïdes, composés analogues du N-acétylcolchinol. Dans un premier temps, une nouvelle voie de synthèse permettant l’accès, de façon racémique, au squelette dibenzoxépine de ces molécules a été mise au point. Elle comprend notamment trois étapes clés, un couplage de Suzuki-Miyaura, une addition de Grignard et une cyclodéshydratation effectuée en présence d’un acide de Brønsted. Par la suite, trois séries d’allocolchicinoïdes de structures variées, que ce soit au niveau du cycle médian oxépine ou des substituants présents sur les noyaux benzéniques, ont été synthétisées. L’activité sur tubuline de la plupart de ces molécules a été évaluée, ce qui a conduit à une rationalisation des relations structure-activité. / N-acetylcolchinol is a semi-synthetic inhibitor of the polymerization of tubulin into microtubules, that showed promising activity as vascular-disrupting agent. However, its toxicity evidenced in phase I clinical trials precluded its further development. This thesis describes the synthesis and biological evaluation of new allocolchicinoids, analogues of N-acetylcolchinol.A racemic synthesis of the dibenzoxepine framework of these compounds was first established. A Suzuki-Miyaura coupling, a Grignard addition and a Brønsted acid-mediated cyclodehydration constituted the key steps of the strategy. Then, three different series of dibenzoxepines have been synthesized, which differ by the nature of the substituent on the oxepine medium ring and on phenyl rings. These new dibenzoxepines were tested against the inhibition of microtubule assembly, leading to a structure-activity relationship study.

Cette thèse apporte une contribution au développement de complexes carbènes N-hétérocycliques-palladium basés sur des calix[4]arènes: leur synthèse, leur caractérisation ainsi que l'évaluation de leur activité catalytique est presenté. Pour cela, un calix[4]arène mono-substitué a été préparé conformément aux procédures classiques, puis les précurseurs de nouveaux ligands NHC ont été obtenus. Subissant l'alkylation avec du n-butylbromide et puis une métallation subséquente avec du palladium et de la pyridine, quatorze nouveaux complexes ont été obtenus. Après les caractérisations complètes en solution et à l'état solide, l'évaluation de l'activité catalytique a été réalisée dans réactions couplage de Suzuki-Miyaura. De bonnes performances ont pu être observées permettant d'obtenir des taux de transformation de 99% avec des quantités de catalyseur descandant jusqu'à 0.08 mol%. L'étude de conformation ainsi que les résultats catalytiques en catalyse n'ont pas permis de mettre en évidence un effet supramoléculaire de la cavité macrocyclique envers le processus de couplage. Dans le but d'orienter le centre catalytique à l'intérieur de la cavité, des contraintes stériques ont été appliquées sur des nouveaux Pd-NHC-complexes. Ainsi des complexes dimeriques de palladium ont été synthétisés et entièrement caractérisés. Plusieurs approches pour construire des linkers intramoléculaires permettant de fixer la conformation ont été énvisagées mais n'ont pas permis à ce jour un gel conformationnel / This thesis will focus on development of N-heterocyclic carbene palladium complexes based on calix[4]arenes: from synthesis, characterization and structural study to evaluation of catalytic activity. A new series of calix[4]arene supported N-heterocyclic carbene palladium complexes was developed and fully characterized. A mono-substituted calix[4]arene was prepared through conventional procedures, following with the attachment of imidazolyl derivative groups to compose the precursors of novel NHCs ligands. Undergoing the alkylation with n-butylbromide and corresponding metallation with palladium and pyridine, original complexes were obtained. After a full characterization in solution and solid state, the evaluation of catalytic activity was undertaken through Suzuki-Miyaura cross-coupling reactions which revealed good performances. The conformational study as well as the catalytic results in catalysis did not allow putting in evidence a supramolecular effect of the macrocycle cavity towards the coupling process. With the aim of localize catalytic center inside of the cavity, steric constrain was involved in the form of new Pd-NHC-complexes. Dimeric Pd complexes were synthesized and fully characterized as well. Several approaches to construct intramolecular linkers for fixing the conformation were elaborated. The conception of ‘flexible steric bulky’ inspired the research on confined structure of calix[4]arene, such as encapsulation and capped configuration. Relative progresses were carried out and discussed

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

La catalyse représente une thématique incontournable de la chimie moderne. Elle occupe une place stratégique dans la recherche de procédés de synthèse plus écologiques et plus économiques en atomes et en énergie. Notre travail réside, d’une part, dans la valorisation d’un biocatalyseur original et, d’autre part, dans la synthèse pallado-catalysée de nouveaux dérivés pyridopyrimidiniques. Dans la première partie, l’utilisation d’un nouveau support naturel préparé à base d’os animal (Animal Bone Meal : ABM) en catalyse hétérogène a été mise en oeuvre, ce qui représente une voie nouvelle et originale, permettant de remplacer les différents catalyseurs solides minéraux connus actuellement et ce, dans diverses réactions classiques de la synthèse organique. Outre les excellents rendements obtenus, les aspects positifs de l’ABM résident dans sa grande stabilité, sa facilité de manipulation et de régénération ainsi que dans l’absence de dangers sur l'environnement. Dans la deuxième partie, une nouvelle stratégie de synthèse simple et efficace de 2,4-di(hét)aryl-pyrido[2,3-d]pyrimidines via un couplage de Suzuki-Miyaura catalysée par le palladium a été développée. Nous avons ensuite étudié la réactivité de diverses 2,4,6-trihalogénopyrido[2,3-d]pyrimidines vis-à-vis des couplages de Suzuki. Cette étude a été étendue à la synthèse de nouvelles 2,4,6-tri(hét)arylpyrido[2,3-d]pyrimidines. / Catalysis is an essential theme of modern chemistry. It occupies a strategic position in the search process more environmentally friendly and more economical energy to atoms and synthesis. Our work lies, on one hand, the development of an original biocatalyst and, secondly, in the pallado-catalyzed synthesis of new derivatives pyridopyrimidiniques. In the first part, the use of a new natural media prepared animal bone (Animal Bone Meal: ABM) based in heterogeneous catalysis has been implemented, which is a new and original way, to replace different solid catalysts currently known minerals and that, in several classical reactions in organic synthesis. In addition to the excellent yields, the positive aspects of ABM lies in its stability, ease of handling and regeneration as well as in the absence of environmental hazards. In the second part, a new strategy for simple and efficient synthesis of 2,4-di(het)aryl-pyrido[2,3-d]pyrimidine via a Suzuki- Miyaura coupling catalyzed by palladium has been developed. We then studied the reactivity of various 2,4,6- trihalogénopyrido[2,3-d]pyrimidine via Suzuki couplings. This study was extended to the synthesis of new 2,4,6- tri(het)arylpyrido[2,3-d]pyrimidine.