RA‐dimer B,a New Dimeric RA‐series Cyclopeptide Incorporating Two Different Types of Cycloisodityrosine Units,from Rubia cordifolia L.

RA‐dimer B, a new cytotoxic RA‐series peptide, was isolated from the roots of Rubia cordifolia L. Its structure was elucidated on the basis of spectroscopic analysis to be a dimeric cyclopeptide composed of deoxybouvardin and allo‐RA‐V. Those two cyclopeptide units are connected by an ether linkage between the phenolic oxygen atom of deoxybouvardin and the ?a carbon atom of Tyr‐6 of allo‐RA‐V. RA‐dimer B was synthesized by the coupling reaction of deoxybouvardin with the boronic acid derivative of allo‐RA‐V, and subsequent deprotection, confirming the relative stereochemistry and establishing the absolute configuration of this peptide. RA‐dimer B showed cytotoxic activity against human promyelocytic leukaemia HL‐60, human colonic carcinoma HCT‐116, and human renal cell carcinoma ACHN cells with IC₅₀ values of 0.59, 0.54, and 0.74 μm , respectively.