Related Experiment Video
Updated: Mar 10, 2026
11:09
Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
11.3K
Stereoselective Peptide Modifications via β-C(sp3)-H Arylations
Biplab Mondal1,2, Brindaban Roy2, Uli Kazmaier1
1Organische Chemie, Universität des Saarlandes , Campus, Geb. C4.2, D-66123 Saarbruecken, Germany.
The Journal of Organic Chemistry
|December 10, 2016
Summary
Palladium-catalyzed peptide modification allows stereoselective beta-arylation without epimerization. This versatile method enables further cross-coupling reactions and C-terminal peptide chain extension.
Area of Science:
- Organic Chemistry
- Peptide Chemistry
- Catalysis
Background:
- Peptide modifications are crucial for developing new therapeutics.
- Stereoselective synthesis is essential for maintaining peptide structure and function.
- Existing methods for peptide arylation often face challenges with epimerization and limited functionalization.
Purpose of the Study:
- To develop a stereoselective palladium-catalyzed beta-arylation method for peptides.
- To demonstrate the compatibility of the method with various amino acids, including phenylalanine, proline, and pipecolinic acid.
- To showcase the utility of the method for further peptide modifications and chain elongation.
Main Methods:
- Palladium-catalyzed cross-coupling reactions.
- Utilizing an 8-amino quinoline (AQ) directing group for regioselectivity.
- Employing stereoselective beta-arylation of peptide substrates.
- Subsequent cross-coupling reactions with functionalized aryl iodides.
- Removal of the AQ directing group for C-terminal deprotection.
Main Results:
- Successful stereoselective beta-arylation of phenylalanine, proline, and pipecolinic acid-containing peptides.
- No epimerization of stereogenic centers in the peptide backbone was observed.
- Demonstrated the introduction of functionalized aryl iodides for subsequent modifications.
- Showcased the efficient removal of the AQ directing group for C-terminal peptide extension.
Conclusions:
- Palladium-catalyzed stereoselective beta-arylation is a robust and versatile tool for peptide modification.
- The method preserves peptide integrity by avoiding epimerization.
- The strategy allows for sequential functionalization and C-terminal chain extension, expanding peptide diversity.
Related Concept Videos
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
18.0K
If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
18.0K
02:35Regioselectivity of Electrophilic Additions-Peroxide Effect
11.4K
In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov’s rule. For example, the addition of hydrogen bromide to 2-methylpropene in the presence of peroxides gives 1-bromo-2-methylpropane. This addition reaction proceeds via a free radical mechanism, which reverses the regioselectivity. The free radical reaction mechanism involves three stages: initiation, propagation, and termination.
11.4K
02:36Regioselectivity and Stereochemistry of Hydroboration
9.6K
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
9.6K
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
9.9K
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.
9.9K
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
4.3K
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.
4.3K
01:30Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)
5.1K
Nucleophilic substitution in aromatic compounds is feasible in substrates bearing strong electron-withdrawing substituents positioned ortho or para to the leaving group. The reaction proceeds via two steps: the addition of the nucleophile and the elimination of the leaving group.
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
5.1K