STUDIES ON RUBIA AKANE (RA) DERIVATIVES .10. BACKBONE TRANSFORMATION OF RA-VII, AN ANTITUMOR CYCLIC HEXAPEPTIDE, THROUGH THIONATION - X-RAYCRYSTAL-STRUCTURE OF [TYR-3-PSI(CH2NH)-ALA-4]RA-VII

RA-VII 1 was thionated with Davy reagent methyl 6 or Davy reagent p-to lyl 7 to afford novel thionopeptides, [Tyr-6-Psi(CS-NH)-D-Ala-1]RA-VII 8, [D-Ala-1-Psi(CS-NH)-Ala-2; Tyr-3-Psi(CS-NH)-Ala-4] RA-VII 9 and [A la-2-Psi(CS-NH)-Tyr-3; Tyr-3-Psi(CS-NH)-Ala-4]RA-VII 10 in addition to known analogues [Tyr-3-Psi(CS-NH)-Ala-4]RA-VII 4 and [Tyr-3-Psi(CS-NH )-Ala-4; Tyr-6-Psi(CS-NH)-D-Ala-1]RA-VII 5. Thionopeptide 4 was reduce d with nickel borohydride to give reduced peptide 11, An X-ray analysi s and an NMR study revealed that compound 11 adopts a different confor mation within the 18-membered-ring moiety from the predominant solutio n conformation of peptide 1 and of thionopeptides 4, 5, 8-10, which wo uld explain the loss in activity of compound 11.