Meeting key synthetic challenges in amanitin synthesis with a new cytotoxic analog: 5'-hydroxy-6'-deoxy-amanitin
| Autor: | Antonio A. W. L. Wong, David M. Perrin, Alla Pryyma, Kaveh Matinkhoo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Chemical Science |
| ISSN: | 2041-6520 |
| Popis: | 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. Elucidating a highly diastereoselective sulfoxidation of S-deoxy-amanitin to afford α-amanitin and a more synthetically accessible analog of near-native toxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|