Total synthesis of quinaldopeptin and its analogues.
The first total synthesis of quinaldopeptin (1) was accomplished. Our approach to the synthesis of 1 includes the solid-phase peptide synthesis of the linear decapeptide 4 followed by macrocyclization and introduction of the quinoline chromophores 2 at a late stage of the synthesis. As for the preparation of 4, a fragment coupling approach was applied considering the C2 symmetrical structure of 1. Chromophore analogues 22 and 23 and desmethyl analogue 27 were also prepared in a manner similar to the synthesis of 1. Synthetic 1 exhibits a strong cytotoxicity with the IC50 value of 3.2 nM. On the other hand, the activity of 23 and 27 was largely reduced.
Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Satoshi
S
Ichikawa
Takuya
T
Okamura
Akira
A
Matsuda
D004448:Echinomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation
C065444:quinaldopeptin; D004448:Echinomycin