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.

中文翻译：

---

RA-XXV和RA-XXVI，来自茜草的双环六肽：结构，合成和构象

从茜草的根中分离出两个在Tyr-5处没有N-甲基的RA系列双环六肽RA-XXV（4）和RA-XXVI（5）。其氨基酸组成和序列分别为通过对MS的分析确定，并通过XRD分析4和RA-XXVI乙酸酯（1）阐明1D和2D NMR数据及其相对结构。的绝对立体化学4用的全合成建立4，和的5，通过与化学相关性4。肽 4和5展出的细胞毒性对人类前骨髓性白血病HL-60（IC ₅₀ = 0.062和0.066μ米，分别地）和人结肠癌HCT-116（IC ₅₀ = 0.028和0.051μ米，分别地）的细胞系。对4和6处于结晶状态的构象结构以及溶液中4和5的构象结构的分析表明，Tyr-5的N-甲基起到使该系列肽优先采用活性构象的作用。