An efficient synthesis of a novel analog of octreotide with an unnatural L-lysine-like tetrazolyl amino acid

作者：Popova Elena A^*; Nikolskaia Sofia K; Gluzdikov Ivan A; Trifonov Rostislav E

来源：Tetrahedron Letters, 2014, 55(36): 5041-5046.

DOI：10.1016/j.tetlet.2014.07.067

• Unnatural amino acid
• 1H-Tetrazole
• L-Lysine
• Cyclic peptides
• Somatostatin analogs

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 ID/2D H-1 and C-13 NMR spectroscopy.

• 出版日期2014-9-3