Related Experiment Video
Updated: Jul 18, 2026
07:11
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Solution-phase synthesis of Aib-containing cyclic hexapeptides.
Tatjana Jeremic1, Anthony Linden, Heinz Heimgartner
1Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich.
Chemistry & Biodiversity
|December 29, 2006
Summary
This study details the synthesis of novel 18-membered cyclohexapeptides containing alpha-aminoisobutyric acid (Aib). Researchers employed solution-phase techniques and X-ray crystallography to characterize these unique peptide structures.
Area of Science:
- Peptide Chemistry
- Organic Synthesis
- Structural Biology
Background:
- Cyclic peptides offer unique structural and functional properties.
- Incorporation of alpha,alpha-disubstituted amino acids like Aib presents synthetic challenges.
Purpose of the Study:
- To synthesize novel 18-membered Aib-containing cyclohexapeptides.
- To characterize the solid-state conformations of these cyclic peptides and their linear precursors.
Main Methods:
- Solution-phase synthesis utilizing the 'azirine/oxazolone method' and classical peptide coupling.
- Deprotection and cyclization using DEPC (diethyl cyanophosphonate).
- X-ray crystallography for conformational analysis.
Main Results:
- Efficient synthesis of four cyclohexapeptides (22, 24a, 24b, 25) in good yields (26-57%).
- Successful incorporation of Aib and Phe(2Me) residues.
- Determination of solid-state conformations for key linear and cyclic peptides.
Conclusions:
- The developed synthetic strategy is effective for producing complex Aib-containing cyclohexapeptides.
- X-ray crystallography provides valuable insights into the conformational preferences of these cyclic structures.
Related Concept Videos
01:29Preparation of Amides
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...
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...
01:22Preparation of 1° Amines: Azide Synthesis
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...
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...
01:28Preparation 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...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...