Diversifying Amino Acids and Peptides via Deaminative Reductive Cross-Couplings Leveraging High-Throughput Experimentation.
J Am Chem Soc
; 145(10): 5684-5695, 2023 03 15.
Article
em En
| MEDLINE
| ID: mdl-36853652
ABSTRACT
A deaminative reductive coupling of amino acid pyridinium salts with aryl bromides has been developed to enable efficient synthesis of noncanonical amino acids and diversification of peptides. This method transforms natural, commercially available lysine, ornithine, diaminobutanoic acid, and diaminopropanoic acid to aryl alanines and homologated derivatives with varying chain lengths. Attractive features include ability to transverse scales, tolerance of pharma-relevant (hetero)aryls and biorthogonal functional groups, and the applicability beyond monomeric amino acids to short and macrocyclic peptide substrates. The success of this work relied on high-throughput experimentation to identify complementary reaction conditions that proved critical for achieving the coupling of a broad scope of aryl bromides with a range of amino acid and peptide substrates including macrocyclic peptides.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Brometos
/
Aminoácidos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article