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A Convergent Total Synthesis of the Death Cap Toxin ?-Amanitin.

ABSTRACT: The toxic bicyclic octapeptide ?-amanitin is mostly found in different species of the mushroom genus Amanita, with the death cap (Amanita phalloides) as one of the most prominent members. Due to its high selective inhibition of RNA polymerase II, which is directly linked to its high toxicity, particularly to hepatocytes, ?-amanitin received an increased attention as a toxin-component of antibody-drug conjugates (ADC) in cancer research. Furthermore, the isolation of ?-amanitin from mushrooms as the sole source severely restricts compound supply as well as further investigations, as structure-activity relationship (SAR) studies. Based on a straightforward access to the non-proteinogenic amino acid dihydroxyisoleucine, we herein present a robust total synthesis of ?-amanitin providing options for production at larger scale as well as future structural diversifications.

SUBMITTER: Siegert MJ

PROVIDER: S-EPMC7154671 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A Convergent Total Synthesis of the Death Cap Toxin α-Amanitin.

Siegert Mary-Ann J MJ Knittel Caroline H CH Süssmuth Roderich D RD

Angewandte Chemie (International ed. in English) 20200206 14

The toxic bicyclic octapeptide α-amanitin is mostly found in different species of the mushroom genus Amanita, with the death cap (Amanita phalloides) as one of the most prominent members. Due to its high selective inhibition of RNA polymerase II, which is directly linked to its high toxicity, particularly to hepatocytes, α-amanitin received an increased attention as a toxin-component of antibody-drug conjugates (ADC) in cancer research. Furthermore, the isolation of α-amanitin from mushrooms as ...[more]

PMID: 31846557

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