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Ce travail a pour objet la synthèse et l’évaluation de molécule bioactives pouvant contribuer efficacement à la lutte contre certains germes infectieux et le cancer. Le premier volet consiste en la synthèse de composés d’origine naturelle, les topopyrones et les calothrixines. En ce qui concerne les topopyrones, cinq hétérodiènes ont été synthétisés et leurs réactivités ont été étudiées face à un diénophile de type naphthoquinone suivant une réaction de cycloaddition [4+2] de Diels-Alder. . Cela a conduit l’édification d’un squelette tétracyclique proche des topopyrones. Quant aux calothrixines, nous avons exploré deux nouvelles voies qui ont abouti à la synthèse de la calothrixine B et d’un analogue bromé. Dans le second volet, en nous basant sur le concept pharmacochimique de juxtaposition d’entités bioactives, nous avons conceptualisé puis synthétisé douze benzimidazolyl-chalcones et une chroménone. Les molécules ainsi obtenues ont fait l’objet d’une évaluation de leurs activités anticancéreuses vis-à-vis de sept lignes cellulaires cancéreuses humaines et une lignée de fibroblastes normaux de la peau humaine. Ces composés ont montré de bonnes activités anticancéreuses quelque soit la lignée. Ces activités sont supérieures à celles de la Roscoviitine mais restent inférieures à celles du Taxol. Cependant, les molécules synthétisées se sont montrées moins toxiques que la molécule de référence Taxol. / This work aims is the synthesis and evaluation of bioactive molecules that can effectively contribute to fight against some infectious germs and the cancer. The first component consists of the synthesis of naturally occurring compounds, topopyrones and calothrixins. With regard to the topopyrones, five heterodienes were synthesized and their reactivities were studied, compared with a naphthoquinone-type dienophile following a Diels-Alder [4+2] cycloaddition reaction. This led to the construction of a tetracyclic skeleton close to topopyrones. As for calothrixins, we explored two new pathways that resulted in the synthesis of calothrixin B and an bromine analogue. In the second part, based on the pharmacochemical concept of juxtaposition of bioactive entities, we conceptualized and synthesized twelve benzimidazolyl-chalcones and one chromenone. The molecules thus obtained were evaluated for their anticancer activities against seven human cancer cell lines and a normal fibroblast line of human skin. These compounds showed good anticancer activities regardless of the line. These activities are superior to those of Roscovitine but lower than those of Taxol. However, the synthesized molecules were less toxic than that of the Taxol reference molecule.

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In recent years the study of benzanthrone and its derivatives has offered the organic chemist a subject for numerous investigations. During the course of a research into the Skraup reactions as applied to anthraquinone, Bally (Ber., 1905, 38, 194) originally prepared benzanthrone by heating anthraquinone with glycerol and sulphuric acid in the presence of a reducing agent. Although two interpretations of this reaction have been put forward, neither is in complete agreement with experimental evidence. The two inter- pretations, however, agree on one point, namely, that the reaction depends upon the condensation of anthrone (I) and acrolein (formed from the glycerol and acid), followed by elimination of water and hydrogen, to yield benzanthrone II.

Controlling gold nanoparticles (GNPs) surface chemistry is a fundamental prerequisite to tailor their properties and envision their assembly into complex nanomaterials from a “bottom-up” approach. Short peptides have been specifically designed to form self-assembled monolayers on GNPs surface and used to increase their stability. However, their structural characterization is often poorly investigated and challenging to assess. This body of work examines different approaches to elucidate the structure and organization of peptide self-assembled monolayers on GNPs. First, the current knowledge and the methods available to characterize the GNPs surface are reviewed. Second, the attempt at using benzophenone-derivative peptides, to provide insights into the molecular organization and compactness of mixed monolayers self-assembled on GNPs, is reported. Under irradiation at 350 nm, the carbonyl group of the benzophenone moiety crosslinks to an adjacent molecule. However, the photo-cross-linking reaction, monitored by FTIR spectroscopy in solution, was not detected on the GNPs surface. Third, to probe the accessibility of a functional group at the GNPs surface, fluorescently labelled peptides, quenched when bound to the gold surface, and bearing a cleavage site for thrombin enzyme at different positions along the chain, were inserted into different peptide self-assembled monolayers on GNPs. The timings of the increase in fluorescence, upon cleavage by thrombin, probed the accessibility, and hence the molecular environment, of the site within the different monolayers investigated. Fourth, a computational model for peptide-capped GNPs was developed using experimentally characterized CALNN- and CFGAILSS-capped GNPs as a benchmark. The molecular dynamics simulations not only reproduced the experimentally observed dependence of the monolayer secondary structure on peptide capping density and on nanoparticle size, but provided also further insights into the monolayers and inter-peptide interactions at the molecular level.

Amino boronate based bifiinctional molecules have the potential to be powerful catalysts. Herein, a number of approaches to the bifimctional benzimidazole catalyst 1 are described, and the synthesis of a number of analogues are explored. Investigations into the potential of 2-(2-boronobenzene)- 2N-n-butylbenzimidazole sodium hydroxide salt 1 as a catalyst for a number of synthetic transformations, including an aza-version of the Baeyer-Villiger reaction (Equation 1), are described The 2-(2-boronobenzene)-N-n-butylbenzimidazole sodium hydroxide salt 1 is shown to be active in the aldol condensation reaction (Equation 2)， Knoevenagel reaction, and evidence for the promotion of the Michael reaction by 1 is presented. The mechanism by which the aldol condensation reaction is promoted by 1 is explored through kinetic studies.

Previous work into the copper catalysed borylation of alkenyl halides has resulted in the synthesis of cyclic Bpin esters. To date however, the reaction has not been applied to the synthesis of saturated heterocycles nor substituted carbocycles. An overview of the literature precedent for reactions involving copper-boryl complexes is provided in the introduction (chapter 1). Investigations into the reaction were undertaken in an attempt to further expand its scope, and the second chapter outlines preliminary results and investigations into the formation of carbocyclic boronate esters. Application of the borylative cyclisation reaction towards the synthesis of heterocyclic boronate esters is also discussed. The third chapter outlines the development of a copper-boryl mediated deallylation reaction, which was developed as a novel method for the selective deprotection of aryl allyl ethers. Attempts to synthesise chromanyl boronate esters are described in chapter 4,followed by conclusions (chapter 5) and experimental data (chapter 6).

A study has been undertaken of some oxidative coupling reactions which are catalysed by copper chloride/pyridine catalyst solutions, gaseous oxygen being the oxidizing agent. The oxidative coupling of thiophenol has been investigated in some detail. It has been discovered that, under certain conditions, one of the products of this reaction is diphenyl thiolsulphinate (PhSOSPh), a potential commercial antioxidant for synthetic rubbers, whereas previously diphenyl disulphide (PhSSPh) was reported to be the only product. The effect of several reaction variables upon both the rate of thiophenol oxidation and the relative yields of products from this reaction have been investigated. In particular, detailed study has been made of the effects of varying mass transfer rates upon the course of this gas-liquid reaction.

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