The synthesis and analysis of the conformation in solution of the dolastatin 3 diastereomer cyclo[‐L‐Pro‐L‐Leu‐D‐(Gln)Thz‐(Gly)Thz‐L‐Val‐]

The cyclic peptide cyclo[‐L‐Pro‐L‐Leu‐D‐(Gln)Thz‐(Gly)Thz‐L‐Val‐] (1a), which is a diastereomer of the antineoplastic agent dolastatin 3 (1b), and contains the unusual thiazole amino acids, was synthesized. All the peptide bonds of the cyclic peptide 1a are trans in solution, and the compound is conformationally homogeneous, as deduced by CD spectroscopy and comprehensive NMR spectroscopy. The conformation was refined by SYBYL molecular force‐field calculations. The saddle‐like conformation contains three intramolecular, but no transannular hydrogen bonds.