Synthesis and study on biological activity of quinoxalyl octadepsipeptide

Abstract

Echinomycin is well known to natural product which shows strong antibiotic activity. Its outer quinoxaline rings have a important role of bis-intercalating around the DNA, and the $C_2$-symmetric peptide also has an interesting biological activity. Connection with the synthesis of echinomycin analogue, new quinoxaline antibiotics which have a cyclic octadepsipeptide but different inner bridge $(-CH_2-S-CH_2-S-CH_2-)$ havw been synthesized. $C_2$-symmetric cyclic octadepsipeptide have been prepared from tradepsipeptide, Cbz-D-Ser[H-Ala-MeCys(Bam)-Me-Val]-OPa, as a key intermediate. New quinoxalyl compounds (66 and 69) were prepared from 55 through 3 steps. Their oxidized forms (67, 68, 70 and 71) were also prepared by oxidation with m-CPBA or dimethyldioxirane. Cytotoxcities of YK-2000 - 2003 against human cancer cell were measured. The YK-2000(66) shows a similar cytotoxicity to echinomycin.