Syntheses of Triostin A Antibiotic and Nucleobase‐Functionalized Analogs as New DNA Binders

Abstract

A total synthesis of the natural product triostin A, wherein the N-methylated depsipeptide scaffold is constructed by solution-phase peptide chemistry followed by disulfide formation and macrocyclization, is described. Finally, the quinoxalines were attached to provide the DNA bisintercalator. Analogs of triostin A were obtained by the successive functionalization of the cyclic depsipeptide with pyrimidine or purine recognition units. The attachment of functional units

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

“…Replacing of quinoxaline intercalating units by different nucleobases led to a wide family of rigid nucleobase-depsipeptide bicyclic conjugates 9 (Fig. 6, up) [34][35][36]. Conjugates were investigated for their DNA-binding potential and for selectivity to the DNA-abasic site.…”

“…Conjugates were investigated for their DNA-binding potential and for selectivity to the DNA-abasic site. Although experiments indicated that mode of conjugate binding differed from that of triostin A bisintercalation, none of the conjugates 9 showed favored recognition of abasic sites [36]. Another modification of triostin A comprised replacement of quinoxalines by adenine and thymine combined by additional functionalization with a metal binding moiety [37] (Fig.…”