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

Abstract

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 ϵa 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 IC values of 0.59, 0.54, and 0.74 μm, respectively.

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

“…The absolute structure of RA‐XXV ( 4 ) was established by the total synthesis of this peptide with d ‐alanine at residue 1, l ‐alanines at residues 2 and 4, and modified l ‐tyrosines at residues 3, 5, and 6. We synthesized peptide 4 on the basis our previous synthesis of allo‐RA‐V, a related compound but with a structurally different cycloisodityrosine unit in which a diphenyl ether bond was formed between the carbon atom at the ϵ position of Tyr‐5 and the phenolic oxygen at the ζ position of Tyr‐6. This synthesis was characterized by the diaryl ether formation of the core cycloisodityrosine unit by copper(II) acetate‐mediated intramolecular phenol/arylboronic acid coupling and the macrocyclization of the linear hexapeptide between the Tyr‐6 and d ‐Ala‐1 residues to construct the 18‐membered cyclopeptide ring.…”

Design and synthesis of analogues of RA-VII—an antitumor bicyclic hexapeptide from Rubiae radix

“…RA-dimer B ( 39 ), the second dimeric RA-series peptide, is composed of deoxybouvardin ( 3 ) and allo-RA-V ( 20 ), and those two cyclopeptides are connected between the phenolic oxygen atom of deoxybouvardin and the εa-carbon atom of the Tyr-6 residue of allo-RA-V ( 20 ) (Fig. 13 ) [ 39 ]. The structure of RA-dimer B ( 39 ) was elucidated on the basis of spectroscopic data, and the synthesis of 39 confirmed the relative stereochemistry and established the absolute configuration of this peptide.…”