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Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration02:34

Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration

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The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
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Cycloaddition Reactions: Overview01:16

Cycloaddition Reactions: Overview

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Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
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Preparation of 1° Amines: Azide Synthesis01:22

Preparation of 1° Amines: Azide Synthesis

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Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
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Preparation of 1° Amines: Gabriel Synthesis01:28

Preparation of 1° Amines: Gabriel Synthesis

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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...
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Amines to Amides: Acylation of Amines01:19

Amines to Amides: Acylation of Amines

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Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
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Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism01:26

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism

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The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
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Updated: Jul 8, 2025

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
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Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

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Ciclización de péptidos nativos, amidación quimioselectiva secuencial en el agua

Huan Chen1, Qiang Zhang1

  • 1Department of Chemistry, State University of New York, University at Albany, Albany, New York 12222, United States.

Journal of the American Chemical Society
|December 11, 2023
PubMed
Resumen
Este resumen es generado por máquina.

La ciclización nativa de péptidos (NPC) simplifica la síntesis de péptidos al permitir la ligadura directa de péptidos no protegidos. Este nuevo método quimioselectivo facilita la preparación eficiente de péptidos cíclicos para terapias rentables.

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Área de la Ciencia:

  • Síntesis Química
  • Química medicinal
  • La bioquímica

Sus antecedentes:

  • La modificación estructural de péptidos y proteínas a través de la síntesis química es un desafío debido a las dificultades en la modificación selectiva de la cadena lateral y el extremo.
  • La ligadura alfa-peptídica directa sin premodificación, especialmente con todos los aminoácidos proteinogénicos, sigue siendo un obstáculo significativo en la síntesis de péptidos.

Objetivo del estudio:

  • Introducir el ciclo nativo de péptidos (NPC), un nuevo método quimioselectivo para la ligadura de péptidos intramoleculares.
  • Para permitir la ciclización directa de péptidos lineales sin protección sin modificación previa.
  • Simplificar la ligadura de péptidos para una preparación cíclica eficiente y aplicaciones terapéuticas.

Principales métodos:

  • La ciclización nativa de péptidos (NPC) utiliza una activación controlada y secuencial de los terminales C y N a través de la modulación del pH.
  • El método funciona en un entorno acuoso, simplificando el proceso de ligadura.
  • NPC permite la ciclización directa de péptidos lineales sin protección.

Principales resultados:

  • El NPC logra la ligadura peptídica intramolecular quimioselectiva sin requerir la premodificación del péptido.
  • El método cicliza con éxito péptidos lineales no protegidos, incluidos aquellos con todos los aminoácidos proteinogénicos en el sitio de ligadura.
  • NPC simplifica la naturaleza de trabajo intensivo de la síntesis de péptidos tradicional.

Conclusiones:

  • La ciclización nativa de péptidos (NPC) ofrece un enfoque simplificado y eficiente para la preparación de péptidos cíclicos.
  • Este método a base de agua reduce la complejidad y el trabajo asociado con la ligadura de péptidos.
  • NPC permite la producción rentable de productos terapéuticos basados en el macrociclo.