<p> The biosynthesis of lycopodine was studied by feeding radioactive acetate, acetoacetato, lysine and pelletierine to Lycopodium tristachyum. Partial degration of the radioactive lycopodine recovered from these experiments revealed specific incorporation of these precursors. The labeling pattern obtained is discussed in the light of the two major blogenetic hypothesis advanced for the Lycopodium alkaloids. </p> <p> The results obtained disproved Conroy's polyacetate hypothesis. They are consistent with the hypothesis that regards these alkaloids derived from lysine and acetate. </p> / Thesis / Doctor of Philosophy (PhD)

Au cours de ce travail, nous nous sommes intéressés dans une première partie à la synthèse biomimétique d’alcaloïdes de type manzamines et plus particulièrement, aux manadomanzamines. Une étude de la réactivité des deux intermédiaires clés de leur biogenèse, les glutaconaldéhydes et les aminopentadiènals, a été entreprise. Ces mêmes molécules ont ensuite été utilisées comme équivalents synthétiques dans une synthèse biomimétique du squelette pentacyclique de la manadomanzamine A. Une seconde partie est consacrée à la préparation d’analogues stables de la pelletiérine en vue d’une synthèse biomimétique d’alcaloïdes du genre Lycopodium. / This work is dedicated to the biomimetic synthesis of complex polycyclic alkaloids namely the manzamine alkaloids and especially to manadomanzamine. The biogenetic hypotheses postulated for these alkaloids are reported in a first introductory chapter. A few examples of manzamine alkaloids biogenesis are described and compared. The second chapter is focused on the reactivity of reactive units (considered as simplified models of two key biosynthetic intermediates, namely glutaconaldehydes and aminopentadienals) resulting from the ring-opening of pyridinium salts, and their implication in natural products synthesis. Particularly detailed are the investigations conducted on 5-dimethylamino-2-methylpenta-2,4-dienal and the condensation of potassium glutaconaldehyde onto a pyridinium salt. The chemistry of these reactive units has been exploited to design several model studies towards the synthesis of pentacyclic indole nucleus of manadomanzamine A, isolated from an Indonesian sponge Acanthostrongylophora sp.. These biomimetic models, elaborated from a biosynthetic intermediate postulated in our biosynthesis hypothesis have culminated in the synthesis of the central pentacyclic indole nucleus. The last chapter reports the preparation of more or less oxidized analogs of pelletierine, the well known alkaloid isolated from Punica granatum. Compounds such as phenyloxazolopelletierine have been prepared and their reactivity investigated in view of the biomimetic synthesis of Lycopodium alkaloids.