Three epimers of a natural cyclic hexapeptide RA-VII were prepared via formation of oxazoles from thioamides or thioimidates of RA-VII followed by hydrolysis. They are the epimers at L-Ala-1, D-Ala-2, and D-Ala-4, respectively. The one having L-Ala-1 adopted trans-cis-trans-trans-trans-trans (t-c-t-t-t-t) amide configurations in the crystal, a type-VI beta-turn for residues 1 - 4 stabilized by one intramolecular hydrogen bond between Ala-4 NH and L-Ala-1 C = O, and in CDCl3 existed as a mixture of six conformers, of which the major conformer was very similar to that in the crystal, but quite different from that of RA-VII in solution. The second epimer, having D-Ala-2 had in the crystalline state t-t-t-t-c-t amide configurations, a gamma-turn at Tyr-3 stabilized by two intramolecular hydrogen bonds between D-Ala-2 NH and Ala-4 C = O and between Ala-4 NH and D-Ala-2 C = O, and existed in CDCl3 as a single conformer, the structure of which was very similar to its crystal structure, and to the crystal structure of peptide 25 except for the backbone and the side chains at residues 1 and 2. The third epimer, having D-Ala-4 had t-c-t-t-c-t amide configurations in the crystal, a type-VI beta-turn for residues 1 - 4 as observed in the first epimer, and in CDCl3 existed in three conformers, of which the major one was similar to that in the crystal but different from that of RA-VII in solution. The three epimers showed very weak cytotoxicity on P-388 leukemia cells, which may be because of their conformational differences from the active conformation of RA-VII.