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Synthèse totale de la quinocarcine.

Abstract : The quinocarcine belongs to the family of tetrahydroisoquinolines, natural products that are potent cytotoxic agents and have many biological activities such qu'antitumorales and antibiotics. His interest in organic and low extraction efficiency of the natural environment have made it an attractive target in organic synthesis. In order to perform the total synthesis of quinocarcine, several strategies have been proposed to build the structure tetracyclic ABCD. These strategies were based on different stages as key reactions of Pictet-Spengler cyclization of Mannich-type, involving N-acyliminium species and various types of nucleophiles, namely malonate, an enamide and an ether silyl enol. The first strategy uses patterned malonate as nucleophile to carry out the Mannich-type reaction has failed to build the ground-diaza-bicyclo [3.2.1]-octane rating. However, the enantioselective synthesis of functionalized tetrahydroisoquinolines has been carried out effectively. On the other hand, an asymmetric synthesis route  acid-carboxy-L-glutamic acid (L-Gla) has been developed in the laboratory. The second strategy we have studied involves nucleophilic type enamides. We met again, problems of responsiveness. Despite our efforts, it has not been possible to activate the function without degradation enamide Genene the reason for desired pyrrolidine by adding on an N-acyliminium. Nevertheless, a synthesis methodology using a Wittig olefination has been developed to prepare α-amino acids containing the motif in β enamide. The third strategy uses a silyl enol ether as a nucleophilic partner to achieve the Mannich reaction. A key intermediate containing the tricyclic motif silyl enol ether has been synthesized. Trials are currently underway to make the last critical step cyclization.
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Mélanie Liron. Synthèse totale de la quinocarcine.. Chimie. Ecole Polytechnique X, 2006. Français. ⟨pastel-00002175⟩

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