Wang X,
Li J,
Hayashi Y.
*
Tohoku University, Sendai, Japan
Highly Sterically Hindered Peptide Bond Formation between α,α-Disubstituted α-Amino
Acids and
N-Alkyl Cysteines Using α,α-Disubstituted α-Amidonitrile.
J. Am. Chem. Soc. 2022;
144: 10145-10150
DOI:
10.1021/jacs.2c02993
Key words
hindered peptide bonds - steric hindrance - alkylcysteines - amidonitriles
Significance
The introduction of unnatural amino acids, such as α,α-disubstituted α-amino acids,
into peptide backbones is important in drug discovery and medicinal chemistry. The
authors have developed a synthetic method for forming such highly hindered peptide
bonds from α,α-disubstituted α-amidonitriles and N-alkylcysteines.
Comment
The method produced hindered peptide bonds in good yields. The reaction of α,α-disubstituted
α-amidonitriles with N-alkylcysteines proceeds in the absence of a coupling reagent.
