Oxidative Coupling Approach to Sarpagine Alkaloids: Total Synthesis of (-)-Trinervine, Vellosimine, (+)-Normacusineâ
B, and (-)-Alstomutinineâ
C.
Angew Chem Int Ed Engl
; 62(28): e202304435, 2023 07 10.
Article
em En
| MEDLINE
| ID: mdl-37160737
ABSTRACT
Sarpagine alkaloids are bioactive indole natural products that contain a highly rigid indole-fused 1-azabicyclo[2.2.2]octane, more than 100 members of which have been identified. Herein, a detailed examination of the intramolecular oxidative coupling between a ketone and a Weinreb amide for assembling the complex 1-azabicyclo[2.2.2]octane core structure of sarpagine family alkaloids is described. Precise late-stage manipulations of the ketone and Weinreb amide enable the divergent syntheses of (-)-trinervine, (+)-vellosimine, (+)-normacusineâ
B, and (-)-alstomutinineâ
C. Other notable transformations of the synthesis featured an aza-Achmatowicz/indole cyclization cascade to generate the azabicyclo[3.3.1]nonane structure, a regioselective elimination reaction to form the ethylidene motif embedded in the (+)-vellosimine and (+)-normacusineâ
B structures, and a diastereoselective indole oxidative rearrangement to form the spirooxindole structure in (-)-alstomutinineâ
C.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Alcaloides
/
Octanos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article