Meeting key synthetic challenges in amanitin synthesis with a new cytotoxic analog: 5′-hydroxy-6′-deoxy-amanitin. Issue 43 (15th October 2020)

• Record Type: Journal Article
• Authors: Pryyma, Alla; Matinkhoo, Kaveh; Wong, Antonio A. W. L.; Perrin, David M.
• Is Part Of: Chemical science. Volume 11:Issue 43(2020)
• Page Start: 11927
• Page End: 11935
• Publication Date: 2020-10-15
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0sc04150e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Elucidating a highly diastereoselective sulfoxidation of S -deoxy-amanitin to afford α-amanitin and a more synthetically accessible analog of near-native toxicity. Abstract : Appreciating the need to access synthetic analogs of amanitin, here we report the synthesis of 5′-hydroxy-6′-deoxy-amanitin, a novel, rationally-designed bioactive analog and constitutional isomer of α-amanitin, that is anticipated to be used as a payload for antibody drug conjugates. In completing this synthesis, we meet the challenge of diastereoselective sulfoxidation by presenting two high-yielding and diastereoselective sulfoxidation approaches to afford the more toxic ( R )-sulfoxide.