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Photochemical Hydrothiolation of Amorphadiene and Formal Synthesis of Artemisinin via a Pummerer Rearrangement
Mario Andrés Gomez Fernandez1, Marllon Nascimento de Oliveira1, Andrea Zanetti2
1Equipe de Chimie Moléculaire, Laboratoire de Génomique, Bioinformatique et Chimie Moléculaire, (GBCM), EA 7528, Conservatoire national des arts et métiers, HESAM Université, 2 rue Conté, 75003 Paris, France.
Abstract:
A new access to artemisinin is reported based on a selective photochemical hydrothiolation of amorphadiene, a waste product of the industrial semisynthetic route. This study highlights the discovery of two distinctive activation pathways under solvent-free conditions or using a photocatalyst promoting H-abstraction. Subsequently, a chemoselective oxidation of the resulting photochemically generated thioether, followed by a Pummerer rearrangement, affords dihydroartemisinic aldehyde, a key intermediate in the synthesis of artemisinin.
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