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Biaryl-Bridged Macrocyclic Peptides: Conformational Constraint via Carbogenic Fusion of Natural Amino Acid Side Chains
- Source :
- The Journal of Organic Chemistry. 77:3099-3114
- Publication Year :
- 2012
- Publisher :
- American Chemical Society (ACS), 2012.
-
Abstract
- A general method for constraining peptide conformations via linkage of aromatic sidechains has been developed. Macrocyclization of suitably functionalized tri-, tetra- and pentapeptides via Suzuki-Miyaura cross-coupling has been used to generate side chain to side chain, biaryl-bridged 14- to 21-membered macrocyclic peptides. Biaryl bridges possessing three different configurations, meta-meta, meta-ortho, and ortho-meta, were systematically explored through regiochemical variation of the aryl halide and aryl boronate coupling partners, allowing fine-tuning of the resultant macrocycle conformation. Suzuki-Miyaura macrocyclizations were successfully achieved both in solution and on solid phase for all three sizes of peptide. This approach constitutes a means of constraining peptide conformation via direct carbogenic fusion of side chains of naturally occurring amino acids such as phenylalanine and tyrosine, and so is complementary to strategies involving non-natural, for example, hydrocarbon, bridges.
- Subjects :
- chemistry.chemical_classification
Molecular Structure
biology
Stereochemistry
Phenylalanine
Aryl
Aryl halide
Organic Chemistry
Stereoisomerism
Peptide
biology.organism_classification
Peptides, Cyclic
Amino acid
Peptide Conformation
Solutions
chemistry.chemical_compound
chemistry
Side chain
Tyrosine
Tetra
Amino Acids
Peptides
Subjects
Details
- ISSN :
- 15206904 and 00223263
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- The Journal of Organic Chemistry
- Accession number :
- edsair.doi.dedup.....6656bb8bd87ffced22af32906fb69bc2