La guttiférone A , appartenant à la famille des PPAPs ou Acyle Phloroglucinol Polycycliques Polyprénylées, est une molécule extraite à partir d’un arbre tropicale, le Symphonia globulifera. Cette matière première est abondante et peut être facilement obtenue. De plus, elle présente de nombreuses activités biologiques, lui conférant un potentiel pharmacologique très intéressant. Trois approches ont été effectuées durant ces travaux. La première fût l’utilisation de microorganismes pour effectuer des biotransformations. L’utilisation de levures a permis de synthétiser la 3,16-oxy-guttiférone A, forme xanthone de la guttiférone. Le second axe a été d’utiliser des outils chimiques pour obtenir des dérivés de la guttiférone A. Dans un premier temps, une vingtaine d’analogues éther et ester du catéchol a été synthétisée, certains de ces composés ont montré un meilleur indice de sélectivité sur les parasites. Une synthèse sélective de xanthone par une réaction de couplage phénolique oxydatif a également été étudiée. Nous avons pu obtenir par cette approche la 3,16-oxy-guttiférone A, la 1,16-oxy-guttiférone A et la 1,12-oxy-guttiférone A. Ces réactions ont aussi donné accès à des dérivés xanthone hydroxylée jamais décrits dans la littérature. Enfin, un travail préliminaire de phytochimie sur les graines et feuilles du Symphonia globulifera a été réalisé, permettant d’isoler des analogues de la guttiférone A, la guttiférone C et D, ainsi que d’autres molécules comme des bisflavonoides et des xanthones. / Guttiferone A, belonging to the PPAPs family (Polycyclic Polyprenylated Acylphloroglucinols), is extracted from a tropical tree called Symphonia globulifera. This raw material is abundant and can be easily obtained. In addition, it has many biological activities, giving it a very interesting pharmacological potential. Three approaches were used in this work. The first was the use of microorganisms to perform biotransformations. The use of yeast allow the synthesis of 3,16-oxy-guttiférone A, a xanthone derivative of guttiferone A. The second theme was the use of chemical tools for guttiferone A derivation. First, twenty ether and ester catechol analogs were synthesized, some of these compounds showed a better selectivity index of parasites. Selective synthesis of xanthone by phenolic oxidative coupling reaction was also studied. We obtained by this approach the 3.16-oxy-guttiferone A, 1,16-oxy-guttiferone A and 1,12-oxy-guttiferone A. These reactions have also provided some hydroxylated xanthone never described before in the literature. Finally, preliminary phytochemical work on seeds and leaves of Symphonia globulifera lead to the isolation of guttiférone A analogues such as guttiférone C and D, as well as other molecules such as bisflavonoides and xanthones.

Modern lifestyle with its lack of exercise and healthy diet often leads to obesity which is accompanied by a decreasing biological effect of insulin and the onset of hyperinsulinemia, and consequently type 2 diabetes. Persistently high levels of insulin stimulate signalling pathways with growth effects; cells thus become more sensitive to mitogenic effects of all growth factors which may even lead to the loss of control over cell proliferation and the rise of various malignancies. Due to a high degree of structure homology of insulin, IGF-I/II as well as particular IR (existing in "mitogenic" IR-A isoform and "metabolic" IR-B isoform) and IGF-1R, there are a number of cross- interaction among hormones and receptors; nevertheless, the biological response may be different during the binding to a receptor. The determination of the crucial structural regions in insulin and IGF which are responsible for binding to the receptors could lead to the evolution of selective insulin analogues with strengthen metabolic effects, or could lead to the evolution of selective antagonism of IGF which would, in turn, suppress the mitogenic effect. The highest overlap is between insulin and IGF-II since both hormones are able to bind to the isoform A of an insulin receptor (IR-A) with a high affinity, and to activate...

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