Synthesis of the Death-Cap Mushroom Toxin α-Amanitin

被引：72

作者：

Matinkhoo, Kaveh ^{[1
]}

Pryyma, Alla ^{[1
]}

Todorovic, Mihajlo ^{[1
]}

Patrick, Brian O. ^{[1
]}

Perrin, David M. ^{[1
]}

机构：

[1] Univ British Columbia, Chem Dept, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2018年 / 140卷 / 21期

基金：

加拿大自然科学与工程研究理事会;

关键词：

PEPTIDE-SYNTHESIS; TRYPTATHIONINE BRIDGES; F-ACTIN; TRYPTOPHAN; PHALLOTOXINS; DERIVATIVES; AMATOXINS; ACID; TRANSCRIPTION; CONFORMATION;

D O I：

10.1021/jacs.7b12698

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

alpha-Amanitin is an extremely toxic bicyclic octapeptide isolated from the death-cap mushroom, Amanita phalloides. As a potent inhibitor of RNA polymerase II, alpha-amanitin is toxic to eukaryotic cells. Recent interest in alpha-amanitin arises from its promise as a payload for antibody drug conjugates. For over 60 years, A. phalloides has been the only source of alpha-amanitin. Here we report a synthesis of alpha-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 sulfoxidation.

引用

页码：6513 / 6517

页数：5

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