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|All Authors / Contributors:||
Jérémy Dufour; Jieping Zhu; Université de Paris-Sud. Faculté des Sciences d'Orsay (Essonne).
|Description:||1 vol. (329 p.) : ill. en noir et en coul. ; 30 cm.|
|Responsibility:||Jérémy Dufour ; [sous la direction de] Jieping Zhu.|
Macrocyclic compounds with an endo aryl-aryl junction have played and are still playing a great role in the discovery of new drugs, thanks to their various and exptionnal bioactivities. The major part or this work has been dedicated to the study towards the syntheses of two families of recently isolated natural biarylic macrocycles : the arylomycines, which are baterial signal peptidase, I inhibitors and the TMC-95, which possess proteasome inhibition properties. Firstly, we he accomplished concise and convergent total syntheses of arylomycins A2 and B2, The key step, i.e. the formation of the strained cyclophane, has been addressed using an intramolecular Suzuki-Miyaura reaction from borylated tripeptides and a domino borylation/intramolecular Suzuki-Miyaura reaction from diiodinated precursors. Then, we worked towards the syntheses of TMC-95, and we particularity focused on the preparation of the Northern oxindolic part by an original and efficient strategy. After several attempts, a route to the dihydrooxindole moiety was validated using an asymmetric rhodium-catalyzed addition of boronic acid onto isatin as the key step. This strategy allowed us to prepare an advanced intermediate that could be used for the total syntheses of TMC-95. Finally, we initiated a project for the synthesis of substituted oxindoles, important building blocks common to many bioactive molecules. For that purpose, a new route was designed using an oxidative palladium-catalyzed C-H bond functionalization of simple anilides.