Two bicyclic hexapeptides, allo-RA-V (4) and neo-RA-V (5), and one cyclic hexapeptide, O-seco-RA-V (6), were isolated from the roots of Rubia cordifolia L. Their gross structures were elucidated on the basis of spectroscopic analysis and X-ray crystallography of compound 5. The absolute stereochemistry of compounds 4 and 5 were established by their total syntheses, and the absolute stereochemistry of compound 6 by chemical correlation with deoxybouvardin (3). Comparison of the 3D structures of highly active RA-VII (1) with less-active compounds 4 and 5 suggests that the orientation of the Tyr-5 and/or Tyr-6 phenyl rings plays a significant role in their biological activity. The isolation of peptides 4-6, along with compound 3, and the comparison of their structures seem to indicate that peptide 6 may be the common precursor to bicyclic peptides 3-5 in the plant.

TwoR A-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 wered etermined 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,a nd that of 5,b yt he chemical correlation with 4.P eptides 4 and 5 exhibited cyto-toxicityt owardh uman promyelocytic leukemia HL-60 (IC 50 = 0.062 and 0.066 mm,r espectively) and human colonic carcinoma HCT-116 (IC 50 = 0.028 and 0.051 mm,r espectively) cell lines. Analysis of the conformationals tructures 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 activec onformation.[a] Prof.Amine 12:P alladium (10 %) on charcoal catalyst (48.9 mg) was added to as olution of 11 (489 mg, 1.22 mmol) in EtOH (13 mL). Then, the reaction mixture was stirred at room temperature under an atmosphere of hydrogen for 20 min. The catalyst was filtered off, the filtrate was concentrated to dryness, and the residue was crystallized from EtOH to give 12 (291 mg) as aw hite crystalline solid. Chromatographic separation (silica gel, CHCl 3 /MeOH 30:1) of ML gave additional 12 (30 mg, total 321 mg, 99 %): m.p. 268-273 8C( decomp.); ½a 25 D =+25 (c = 0.72 in CHCl 3 ); 1 HNMR

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