Studies on Rubia akane(RA) derivatives. Part 10. Backbone transformation of RA-VII, an antitumour cyclic hexapeptide, through thionation. X-Ray crystal structure of [Tyr-3-Ψ(CH2NH)-Ala-4]RA-VII

Abstract

RA-VII 1 was thionated with Davy reagent methyl 6 or Davy reagent p-tolyl 7 to afford novel thionopeptides, [Tyr-6-Ψ(CS-NH)-D-Ala-1]RA-VII 8, [D-Ala-1-Ψ(CS-NH)-Ala-2; Tyr-3-Ψ(CS-NH)-Ala-4]RA-VII 9 and [Ala-2-Ψ(CS-NH)-Tyr-3; Tyr-3-Ψ(CS-NH)-Ala-4]RA-VII 10 in addition to known analogues [Tyr-3-Ψ(CS-NH)-Ala-4]RA-VII 4 and [Tyr-3-Ψ(CS-NH)-Ala-4; Tyr-6-Ψ(CS-NH)-D-Ala-1]RA-VII 5. Thionopeptide 4 was reduced with nickel borohydride to give reduced peptide 11. An X-ray analysis and an NMR study revealed that compound 11 adopts a different conformation within the 18-membered-ring moiety from the predominant solution conformation of peptide 1 and of thionopeptides 4, 5, 8–10, which would explain the loss in activity of compound 11.