RA‐XXV and RA‐XXVI, Bicyclic Hexapeptides from Rubia cordifolia L.: Structure, Synthesis, and Conformation.

Two RA‐series bicyclic hexapeptides, RA‐XXV (4) and RA‐XXVI (5), which have no N‐methyl group at Tyr‐5, were isolated from the roots of Rubia cordifolia L. Their amino acid compositions and sequences were determined by interpretation of MS, and 1D and 2D NMR data and their relative structures were elucidated by XRD analysis of 4 and RA‐XXVI acetate (6). The absolute stereochemistry of 4 was established by the total synthesis of 4, and that of 5, by the chemical correlation with 4. Peptides 4 and 5 exhibited cytotoxicity toward human promyelocytic leukemia HL‐60 (IC50=0.062 and 0.066 μm, respectively) and human colonic carcinoma HCT‐116 (IC50=0.028 and 0.051 μm, respectively) cell lines. Analysis of the conformational structures of 4 and 6 in the crystalline state and those of 4 and 5 in solution revealed that the N‐methyl group at Tyr‐5 functions to make this series of peptides preferentially adopt the active conformation. The eye of Ra: Two RA‐series bicyclic hexapeptides, RA‐XXV and RA‐XXVI, which have no N‐methyl group at Tyr‐5, were isolated from the roots of Rubia cordifolia L. and their absolute structures were established by synthetic methods. Investigation of their conformational properties and cytotoxic activity revealed that the N‐methyl group at Tyr‐5 is necessary for this series of peptides to take the active conformation preferentially. [ABSTRACT FROM AUTHOR]