Síntesis total de (-) -Mandelalido A que explota la química de relevo de aniones (ARC): identificación de un protocolo de acoplamiento cruzado ARC/CuCN de tipo II

Video Experimental Relacionado

Updated: Mar 24, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Published on: August 22, 2018

Minh H Nguyen¹, Masashi Imanishi¹, Taichi Kurogi¹

¹Department of Chemistry, Laboratory for Research on the Structure of Matter, and Monell Chemical Senses Center, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.

Journal of the American Chemical Society

|March 9, 2016

Resumen

La química de relevo aniónico (ARC) permitió la síntesis total del macrolido (-) -mandelalido A marino citotóxico. Esta táctica de unión multicomponente ensambló rápidamente fragmentos moleculares complejos a partir de bloques de construcción simples con un alto control estereoquímico.

Área de la Ciencia:

Química orgánica
Química sintética
Química medicinal

Sus antecedentes:

Los productos naturales marinos, como los macrólidos, son una rica fuente de compuestos citotóxicos.
(-) -Mandelalida A es un macrolido marino altamente citotóxico con una estructura molecular compleja.
Se necesitan estrategias sintéticas eficientes para acceder a estos productos naturales complejos para su estudio posterior.

Objetivo del estudio:

Desarrollar y emplear la química de relés de aniones (ARC) para la síntesis total de (-) -mandelalida A.
Mostrar el ARC como una estrategia de acoplamiento versátil y escalable para la síntesis de moléculas complejas.
Demostrar la utilidad del ARC en el ensamblaje de fragmentos moleculares con un alto control estereoquímico.

Principales métodos:

Utilizó una nueva táctica de acoplamiento cruzado tipo II ARC / CuCN para la síntesis del hemisferio norte.
Utilizó una unión ARC de cuatro componentes de tipo I de alta eficiencia para la construcción del hemisferio sur.
Bloques de construcción simples y fácilmente disponibles para la síntesis convergente.

Principales resultados:

Se ha logrado con éxito la síntesis total de (-) -mandelalida A.
Demostró la efectividad de ARC en la construcción de arquitecturas moleculares complejas.
Consiguió un excelente control estereoquímico durante toda la síntesis.

Conclusiones:

La química de relés de aniones (ARC) es una táctica de unión multicomponente poderosa y efectiva para la síntesis de moléculas complejas.
El ARC proporciona una vía rápida y escalable para acceder a valiosos productos naturales marinos como la (-) mandelalida A.
La estrategia sintética destaca el potencial de ARC para generar diversos fragmentos moleculares con precisión.

Más Videos Relacionados

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Published on: June 13, 2022

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

Published on: August 16, 2018

Videos de Conceptos Relacionados

Alkylation of β-Diester Enolates: Malonic Ester Synthesis

Alkylation of β-Diester Enolates: Malonic Ester Synthesis

Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.

Preparation of 1° Amines: Gabriel Synthesis

Preparation of 1° Amines: Gabriel Synthesis

Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...

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.

[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.

Acid Halides to Amides: Aminolysis

Acid Halides to Amides: Aminolysis

Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...