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Preparation of Amides01:29

Preparation of Amides

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Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
4.1K

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Solid-Phase Synthesis of Oxetane Modified Peptides.

Jonathan D Beadle1, Astrid Knuhtsen2, Alex Hoose2

  • 1Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U.K.

Organic Letters
|June 7, 2017
PubMed
Summary

Researchers developed a novel method using solid-phase peptide synthesis (SPPS) to create peptidomimetics with oxetane rings. This technique allows for the incorporation of modified building blocks into peptide chains, yielding high-purity peptide derivatives.

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Area of Science:

  • Medicinal Chemistry
  • Organic Synthesis
  • Peptide Chemistry

Background:

  • Solid-phase peptide synthesis (SPPS) is a cornerstone for creating peptide-based therapeutics and research tools.
  • Incorporating non-natural modifications into peptide backbones can enhance stability and alter biological activity.
  • Developing efficient methods for synthesizing modified peptides is crucial for advancing drug discovery.

Purpose of the Study:

  • To develop a novel method for synthesizing peptidomimetics containing oxetane rings within the peptide backbone.
  • To demonstrate the utility of oxetane-containing dipeptide building blocks in conventional Fmoc SPPS.
  • To produce high-purity backbone-modified peptide derivatives for potential therapeutic applications.

Main Methods:

  • Synthesis of oxetane-containing dipeptide building blocks in solution through a three-step process.
  • Integration of these modified building blocks into peptide chains using standard Fmoc SPPS.
  • Purification and characterization of the resulting backbone-modified peptides.

Main Results:

  • Successfully synthesized oxetane-containing dipeptide building blocks.
  • Demonstrated efficient incorporation of these building blocks into growing peptide chains via Fmoc SPPS.
  • Produced a range of high-purity peptidomimetics, including modified bradykinin, Met-enkephalin, and Leu-enkephalin.

Conclusions:

  • The described methodology provides a robust route for incorporating oxetane rings into peptide backbones.
  • This approach enables the synthesis of novel peptidomimetics with potential for improved pharmacological properties.
  • The developed technique is versatile and applicable to various peptide sequences.