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Related Concept Videos

Preparation of Amines: Reductive Amination of Aldehydes and Ketones01:38

Preparation of Amines: Reductive Amination of Aldehydes and Ketones

3.2K
Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.
3.2K
Amides to Amines: LiAlH4 Reduction01:20

Amides to Amines: LiAlH4 Reduction

5.2K
Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
5.2K
Amines to Amides: Acylation of Amines01:19

Amines to Amides: Acylation of Amines

2.7K
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...
2.7K
Preparation of 1° Amines: Azide Synthesis01:22

Preparation of 1° Amines: Azide Synthesis

4.2K
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...
4.2K
Preparation of Amines: Reduction of Amides and Nitriles01:13

Preparation of Amines: Reduction of Amides and Nitriles

2.6K
Nitriles can be reduced to primary amines using reducing agents like lithium aluminum hydride or catalytic hydrogenation. The reduction introduces an amino group with an extra carbon in the skeleton. Nitriles are formed from the reaction between alkyl halides and sodium cyanide through the SN2 mechanism. Primary alkyl halides are the preferred substrates to prepare nitriles.
Amides can be reduced to primary, secondary, and tertiary amines using catalytic hydrogenation, active metals like Fe,...
2.6K
Preparation of 1° Amines: Gabriel Synthesis01:28

Preparation of 1° Amines: Gabriel Synthesis

3.8K
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...
3.8K

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Related Experiment Video

Updated: Sep 21, 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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Peptide macrocyclisation via late-stage reductive amination.

Hayden J Bell1,2, Lara R Malins1,2

  • 1Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia. lara.malins@anu.edu.au.

Organic & Biomolecular Chemistry
|May 27, 2022
PubMed
Summary
This summary is machine-generated.

This study introduces a novel two-component reductive amination method for synthesizing peptide macrocycles. This approach efficiently creates macrocyclic peptides with embedded pyridine motifs, offering new possibilities for peptide modification.

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An Inexpensive Adaptation of a Commercial Microwave Reactor for Solid Phase Peptide Synthesis
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An Inexpensive Adaptation of a Commercial Microwave Reactor for Solid Phase Peptide Synthesis
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Area of Science:

  • Organic Chemistry
  • Medicinal Chemistry
  • Biochemistry

Background:

  • Peptide macrocycles are important scaffolds in drug discovery and chemical biology.
  • Existing methods for macrocyclization can be complex and require protecting groups.
  • Developing efficient and versatile methods for peptide macrocycle synthesis is crucial.

Purpose of the Study:

  • To develop a novel two-component reductive amination strategy for peptide macrocycle synthesis.
  • To utilize readily available proteinogenic amine nucleophiles without protection.
  • To introduce versatile handles for post-cyclization modifications.

Main Methods:

  • A two-component reductive amination reaction between unprotected peptides and 2,6-pyridinedialdehyde linkers.
  • Reactions performed in aqueous media, leveraging the reactivity of α-amine and side chain amine motifs.
  • Post-cyclization modification using copper-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry on dialdehyde staples.

Main Results:

  • Successful synthesis of peptide macrocycles with backbone-embedded pyridine motifs.
  • Demonstrated efficiency of the two-fold reductive amination in aqueous conditions.
  • Incorporation of azide and alkyne handles for subsequent functionalization via CuAAC.

Conclusions:

  • The reported method provides an efficient and versatile approach to peptide macrocycle synthesis.
  • This strategy simplifies macrocyclization by avoiding peptide protection steps.
  • The incorporated handles allow for facile diversification of the synthesized macrocycles.