Synthesis of the Death-Cap Mushroom Toxin α-Amanitin.

α-Amanitin is an extremely toxic bicyclic octapeptide isolated from the death-cap mushroom, Amanita phalloides. As a potent inhibitor of RNA polymerase II, α -amanitin is toxic to eukaryotic cells. Recent interest in α -amanitin arises from its promise as a payload for antibody -- drug conjugates. For over 60 years, A. phalloides has been the only source of α -amanitin. Here we report a synthesis of α -amanitin, which surmounts the key challenges for installing the 6-hydroxy-tryptathionine sulfoxide bridge, enantioselective synthesis of (2S,3R,4R)- 4,5-dihydroxy-isoleucine, and diastereoselective sulfoxida-tion. [ABSTRACT FROM AUTHOR]