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Syntheses of Triostin A Antibiotic and Nucleobase‐Functionalized Analogs as New DNA Binders
Author(s) -
Kumar Ray Anmol,
Diederichsen Ulf
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900530
Subject(s) - chemistry , depsipeptide , nucleobase , combinatorial chemistry , intercalation (chemistry) , pyrimidine , dna , stereochemistry , natural product , hydrogen bond , organic chemistry , molecule , biochemistry
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 was achieved by the orthogonal protection of the respective side chain amino functionalities. The nucleobase‐functionalized triostin analogs have the potential to recognize double‐stranded DNA by hydrogen bonding. The interaction with DNA was investigated by UV spectroscopy and fluorescence intercalator displacement. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)