Collect. Czech. Chem. Commun. 2001, 66, 923-932

Epimerization During Coupling to the Unnatural Amino Acid in Solid Phase Peptide Synthesis

Zhenyu Zhang, Arthur Van Aerschot, Patrick Chaltin, Roger Busson and Piet Herdewijn*

Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, Leuven, 3000, Belgium


Extensive epimerization was observed during the coupling of Fmoc-L-Trp(Boc) and Fmoc-L-Pro to D-Ual, a synthetic α-amino acid with a nucleobase in the side chain. This unnatural amino acid was used extensively in the construction of nucleic acids recognition libraries. Reaction protocols based on the use of DIC-HOAt-DIEA mixture without preactivation of the coupling mixture has been proven to suppress the epimerization reaction significantly.

Keywords: Solid phase synthesis; Epimerization; Peptides; Nucleobases; PNA; Uracil; Amino acids.

References: 13 live references.