A new cyclic octreotide-like octapeptide was prepared by incorporation of an unnatural tetrazolyl amino
acid, an analog of Fmoc-L-lysine, into the peptide chain. The new tetrazolyl amino acid, (S)-2-{[2-(9H-fluoren-
9-yl)acetoxy]amino}-6-(1H-tetrazol-1-yl)hexanoic acid, was obtained by azidation of Fmoc-L-lysine
trifluoroacetate with sodium azide in the presence of triethyl orthoformate in glacial acetic acid. The
linear peptide sequence was prepared using efficient Fmoc/t-Bu solid-phase peptide synthesis (SPPS).
Cyclization of the octapeptide was carried out via oxidation with iodine. The structure and purity of
the cyclic octapeptide were confirmed by LC–MS, MALDI-TOF MS/MS analysis as well as 1D/2D 1H and
13C NMR spectroscopy.