Studies on the Enantioselective Synthesis of E-Ethylidene-bearing Spiro[indolizidine-1,3′-oxindole] Alkaloids

A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3′-oxindole] framework present in a large number of oxindole alkaloids, with a <i>cis</i> H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an <i>E</i>...

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Detalles Bibliográficos
Autores: Yayik, Nihan, Pérez, Maria, Molins, Elies, Bosch, Joan, Amat, Mercedes
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/227909
Acceso en línea:http://hdl.handle.net/10261/227909
Access Level:acceso abierto
Palabra clave:Oxindoles
Alkaloids
Spiro compounds
Ethylidene
Descripción
Sumario:A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3′-oxindole] framework present in a large number of oxindole alkaloids, with a <i>cis</i> H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an <i>E</i>-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the <i>E</i>-ethylidene substituent by acetylation at the α-position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(<i>S</i>)-geissoschizol oxindole has been prepared.