Photo-induced synthesis of chiral galaxamide analogs and the biological activities against human tumor cells

Abstract

Two chiral analogs of galaxamide were synthesized by a photoinduced cyclization reaction.

Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents

“…Galaxamide is defined as cyclo-(L-Leu-L-N-Me-Leu-L-Leu-L-Leu-L-N-Me-Leu Leu). The structural modification of galaxamide is initiated by splitting the amide bond the peptide sequence, followed by the introduction of phthalimide and photoinduced clization of linear peptides, as reported in our previous research [12,13]. In the pres study, the photoinduced substrate linear peptide is prepared by a liquid-phase metho as shown in Scheme 1.…”

“…N-Me-leucine used here was prepared by adopting the t-BOC-l cine and iodomethane as raw materials in the presence of TEA. Then, the nitrogen-term nal amino groups were masked with phthaloylglycyl chloride to obtain N-phthalimid During the photoinduced process, the chain-like molecule (linear peptide) was excited and formed intramolecular zwitterionic biradicals after the departure of MeOSiMe 3 , and then the donator-and acceptor-free radicals at each end connected with each other to produce the cyclic compound [12,13]. After coupling, the C 3 carbonyl peak of phthalimido at δ 180 ppm disappeared in the 13 C NMR spectrum, followed by a new sp 3 hybridized C 3 peak at δ 85 ± 5 ppm, which is the characteristic NMR peak position of C 3 after the IPETC reaction.…”

“…Meanwhile, N-methylation has been reported to be able to influence the bioactivity of peptides significantly due to the steric hinder and the blocking of the formation of hydrogen bonds between the polypeptides and proteolytic enzyme cleavage sites [10,11]. Our group has modified galaxamide recently by inserting an unnatural isoindolinone fragment groups and removing the methyl groups [12]. We found that after removing the two N-methyl groups of galaxamide and introducing a rigid isoindolinone fragment into the skeleton by intramolecular photoinduced single electron transfer cyclization reaction (IPETC), the obtained cyclic peptide analogs still maintained significant antitumor activity against HepG-2 cells, and the peptide containing the D-leucine fraction showed stronger bioactivity than that with L-leucine residues, suggesting that the isoindolinone fragment together with the D-residues may play an important role in treatment.…”

Photo-induced synthesis, structure and in vitro bioactivity of a natural cyclic peptide Yunnanin A analog

“…Our group has successfully synthesized some analogs of natural cyclic peptides Sansalvamide A, Fenestin A and Galaxamide by this method. [17][18][19] We found that the synthesis of cyclopeptides analogs by SET would produce optical pure cyclopeptides in our previous research, which could be regarded as a useful tool to prepare cyclic peptides with specic conformations.…”

Photo-induced synthesis and antitumor activity of marine zygosporamide analogs containing the isoindolinone fragment

“…2). In our previous studies, we also found that the chemical environment of hydrogen atoms on the phthaloyl group was changed after cyclization, 14 which could be ascribed to the + Si(CH 3 ) 3 group leaving and the integration of the phthaloyl carbonyl chromophore, leading to the disappearance of the symmetric hydrogen atom of phthaloyl. Meanwhile, the shielding effect of the cyclic peptide skeleton thus shifted the resonance upfield.…”