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Síntesis de la (-) picrotoxina por activación de enlaces fuertes en etapa tardía

Steven W M Crossley¹, Guanghu Tong¹, Michael J Lambrecht¹

¹Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

Journal of the American Chemical Society

|June 24, 2020

Resumen

Se desarrolló una nueva y eficiente síntesis del compuesto neurotóxico (-) -picrotoxinina (PXN). Este método utiliza una nueva estrategia de dimetilación para construir el núcleo cíclico y formar la estructura final de lactona.

Área de la Ciencia:

Química orgánica
Síntesis de productos naturales
La neurociencia

Sus antecedentes:

(-) La picrotoxina (PXN) es una neurotoxina potente y una herramienta de investigación valiosa.
Las rutas sintéticas existentes para PXN a menudo son largas y carecen de control estéreo.
La síntesis eficiente y estereoselectiva de productos naturales complejos es crucial para la investigación en biología química.

Objetivo del estudio:

Desarrollar una síntesis concisa y estereocontrolada de (-) -picrotoxinina (PXN).
Explorar una nueva estrategia sintética que emplee un grupo dimetilo geminal para la construcción del núcleo.
Permitir una mayor investigación sobre la actividad biológica y los mecanismos de la PXN.

Principales métodos:

Formación regioselectiva y estereoselectiva del núcleo ciclico [4.3.0] a través de un grupo dimetilo geminal simetrizante en C5.
Formación selectiva de enlaces C-O facilitada por la dimetilación C5.
Clivadas estratégicas de enlaces C-C y C-H para convertir el grupo gem-dimetilo en la lactona C15.

Principales resultados:

Se ha conseguido una síntesis total de (-) -picrotoxinina muy concisa y estereocontrolada.
Demostró la utilidad del grupo dimetilo geminal para la construcción eficiente de núcleos ciclicos.
Se estableció una nueva vía para la formación de lactona a partir del sustituyente C5.

Conclusiones:

La vía sintética reportada ofrece un avance significativo en la preparación de (-) -picrotoxinina.
Esta síntesis eficiente proporciona una fuente confiable de PXN para estudios neurobiológicos.
La estrategia sintética empleada tiene aplicaciones potenciales para otras síntesis complejas de productos naturales.

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