Video Experimental Relacionado

Updated: Jul 17, 2025

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy

Published on: November 9, 2019

Síntesis de (-) -Cotilenol, un componente de pegamento molecular del tipo 14-3-3

Stephen I Ting¹, Dylan W Snelson^1,2, Tucker R Huffman^1,2

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

Journal of the American Chemical Society

|September 8, 2023

Resumen

Los investigadores desarrollaron una nueva síntesis de 10 pasos para (-) -cotilenol, una molécula valiosa dirigida a la red de interacción proteína-proteína (PPI). Este método permite la creación de compuestos relacionados para la investigación terapéutica.

Área de la Ciencia:

Química orgánica
Química medicinal
Síntesis Química

Sus antecedentes:

Las moléculas pequeñas que modulan las interacciones proteína-proteína 14-3-3 (IPP) son cruciales para las terapias y las herramientas de investigación.
El acceso a los pegamentos moleculares de la clase 14-3-3 PPI ha sido limitado, lo que requiere nuevas estrategias sintéticas para los análogos.

Objetivo del estudio:

Desarrollar una síntesis química práctica y concisa para el (-) -cotilenol.
Establecer una vía sintética versátil para la generación de diversos análogos y bibliotecas de compuestos de la clase de los cotilénidos.

Principales métodos:

Se empleó una síntesis asimétrica de 10 pasos, con una estructura de núcleo 5-8-5.
Las reacciones clave incluyeron un acoplamiento de fragmentos de Liebeskind-Srogl y una cascada de Claisen-ene en tándem.
Se utilizó el control de la estereoquímica y la funcionalización en etapa tardía.

Principales resultados:

El (-) -cotilenol se sintetizó de manera eficiente a través de la ruta de 10 pasos desarrollada.
La síntesis superó con éxito un obstáculo estérico significativo en un paso clave de acoplamiento de fragmentos.
La cascada de Claisen-ene en tándem construyó efectivamente el anillo de ocho miembros.

Conclusiones:

La síntesis reportada proporciona una entrada práctica para el (-) -cotilenol y las moléculas relacionadas.
Esta ruta facilita la exploración de los moduladores 14-3-3 PPI para el descubrimiento de fármacos.
La metodología es susceptible a la síntesis de bibliotecas enfocadas para estudios de relaciones estructura-actividad.

Más Videos Relacionados

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

Published on: October 30, 2018

Videos de Conceptos Relacionados

[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.

[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement

[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement

The Cope rearrangement is classified as a [3,3] sigmatropic shift in 1,5-dienes, leading to a more stable, isomeric 1,5-diene. The reaction involves a concerted movement of six electrons, four from two π bonds and two from a σ bond, via an energetically favorable chair-like transition state.

Diels–Alder Reaction Forming Cyclic Products: Stereochemistry

Diels–Alder Reaction Forming Cyclic Products: Stereochemistry

The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.

Vicinal Diols via Reductive Coupling of Aldehydes or Ketones: Pinacol Coupling Overview

Vicinal Diols via Reductive Coupling of Aldehydes or Ketones: Pinacol Coupling Overview

Wilhelm Rudolph Fittig discovered the pinacol coupling reaction in 1859. It is a radical dimerization reaction and involves the reductive coupling of aldehydes or ketones in the presence of hydrocarbon solvent to yield vicinal diols.

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.

Structure of Conjugated Dienes

Structure of Conjugated Dienes

Introduction
Conjugated dienes are compounds characterized by the presence of alternating double and single bonds. In a conjugated system like 1,3-butadiene, the unhybridized 2p orbital on each carbon overlaps continuously, allowing the π electrons to be delocalized across the entire molecule. In contrast, this type of overlap does not occur in cumulated and isolated dienes, such as 2,3-pentadiene and 1,4-pentadiene, respectively. Instead, the π electrons remain localized between the double...