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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
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Síntesis total del (+) -amphidinolido A. Elucidación de la estructura y finalización de la síntesis
Barry M Trost1, Paul E Harrington, John D Chisholm
1Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Journal of the American Chemical Society
|September 30, 2005
Resumen
La síntesis total de macrolide (+) -amphidinolide A citotóxico se logró mediante el acoplamiento catalizado por rutenio. Este método confirmó la correcta estereoquímica del producto natural a través del análisis de RMN de diastereómeros sintéticos.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- Síntesis de Productos Naturales.
- Biología Química Biología química.
Sus antecedentes:
- (+) -Amphidinolide A es un macrolido citotóxico con una compleja estructura de anillo de 20 miembros.
- Elucidar la estereoquímica precisa de estos productos naturales es crucial para comprender su actividad biológica y para los esfuerzos sintéticos.
Objetivo del estudio:
- Para lograr la síntesis total de (+) -amphidinolide A.
- Para confirmar la estructura propuesta y la estereoquímica relativa del producto natural.
- Desarrollar estrategias sintéticas eficientes para macrolides complejos.
Principales métodos:
- El acoplamiento alqueno-alqueno catalizado por rutenio se empleó para formar el enlace C15-C16, construyendo el anillo de macrolactona de 20 miembros.
- Síntesis de varios diastereómeros del anphidinolide A a partir de una estructura propuesta.
- Análisis de desplazamiento químico por resonancia magnética nuclear (RMN) para comparar los isómeros sintéticos con el producto natural.
Principales resultados:
- El éxito de la síntesis total de (+) -amphidinolide A.
- Identificación de errores estructurales en la estereoquímica inicialmente reportada mediante el análisis de desviaciones en los desplazamientos químicos de RMN.
- Los datos espectroscópicos del compuesto sintético mostraron una excelente concordancia con el material natural, confirmando la estructura revisada.
Conclusiones:
- La estructura y la estereoquímica relativa de (+) -amphidinolide A se han establecido definitivamente a través de la síntesis total y el análisis de RMN.
- La ruta sintética proporciona un método confiable para acceder al anphidinolide A y sus análogos.
- Este trabajo valida la utilidad del análisis de desplazamiento químico de RMN en la aclaración de la estructura y la asignación estereoquímica de productos naturales complejos.
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