Isolation, structure determination, and synthesis of allo-RA-V and neo-RA-V, RA-series bicyclic peptides from Rubia cordifolia L.
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.
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Yukio
Y
Hitotsuyanagi
Masumi
M
Odagiri
Saori
S
Kato
Jun-ichi
J
Kusano
Tomoyo
T
Hasuda
Haruhiko
H
Fukaya
Koichi
K
Takeya
D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D045470:Rubia / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry
D010456:Peptides, Cyclic; D014443:Tyrosine; C043547:RA V; C043548:RA VII