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