Total Synthesis and Structural Plasticity of Kratom Pseudoindoxyl Metabolites.
Angew Chem Int Ed Engl
; 62(35): e202303700, 2023 08 28.
Article
em En
| MEDLINE
| ID: mdl-37332089
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.
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Base de dados:
MEDLINE
Assunto principal:
Mitragyna
/
Alcaloides de Triptamina e Secologanina
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article