Dorow RL,
*,
Gingrich DE.
DuPont Pharmaceuticals Company, Wilmington, USA
A Novel, One-Pot Preparation of
N-Methyl-α-Amino Acid Dipeptides from Oxazolidinones and Amino Acids.
Tetrahedron Lett. 1999;
40: 467-470
DOI:
10.1016/S0040-4039(98)02426-5
Key words
oxazolidinones -
N-methyl dipeptides - amino acid esters
Significance
N-Methyl peptides play a crucial role in peptide drug discovery. This N-methyl peptide is especially useful for the improvement of biological properties
such as target affinity, proteolytic stability and membrane permeability as well as
the alteration of the conformational rigidity and hydrophobicity of the peptides.
In 1999, R. L. Dorow and co-workers developed a one-pot synthesis of N-methyl-α-amino acid dipeptides from oxazolidinones and amino acids.
Comment
A series of amino-acid-derived oxazolidinones reacted smoothly with the amino acid
esters to produce N-hydroxymethyl dipeptides, which were treated with TFAA and Et3SiH to produce the corresponding N-methyl dipeptides in good yields. This one-pot protocol is a practically simple and
highly efficient method to produce various N-methyl peptides.
