Total Synthesis and Structural Plasticity of Kratom Pseudoindoxyl Metabolites **

Abstract: Mitragynine pseudoindoxyl, a kratom metabolite, has attracted increasing attention due to its favorable side effect profile as compared to conventional opioids. Herein, we describe the first enantioselective and scalable total synthesis of this natural product and its epimeric congener, speciogynine pseudoindoxyl. The characteristic spiro‐5‐5‐6‐tricyclic system of these alkaloids was formed through a protecting‐group‐free cascade relay process in which oxidized tryptamine and secologanin analogues were used. Furthermore, we discovered that mitragynine pseudoindoxyl acts not as a single molecular entity but as a dynamic ensemble of stereoisomers in protic environments; thus, it exhibits structural plasticity in biological systems. Accordingly, these synthetic, structural, and biological studies provide a basis for the planned design of mitragynine pseudoindoxyl analogues, which can guide the development of next‐generation analgesics.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Total Synthesis and Structural Plasticity of Kratom Pseudoindoxyl Metabolites ** ; day:18 ; month:07 ; year:2023 ; extent:9 ; Angewandte Chemie / International edition. International edition ; (18.07.2023) (gesamt 9)

Contributors, Places and Time

• Creator: Angyal, Péter ; Hegedüs, Kristóf ; Mészáros, Bence Balázs ; Daru, János ; Dudás, Ádám ; Galambos, Anna Rita ; Essmat, Nariman ; Al‐Khrasani, Mahmoud ; Varga, Szilárd ; Soós, Tibor

Further information

• DOI: 10.1002/anie.202303700
• URN: urn:nbn:de:101:1-2023071815251034549665
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:58 AM CEST