Premium
Synthesis, Structure, and Cytotoxicity of Urukthapelstatin A Polyazole Cyclopeptide Analogs
Author(s) -
Oberheide Ansgar,
Schwenk Sebastian,
Ronco Cyril,
Semmrau Lisa Maria,
Görls Helmar,
Arndt HansDieter
Publication year - 2019
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.201900206
Subject(s) - chemistry , stereochemistry , natural product , tripeptide , oxazole , cytotoxicity , depsipeptide , cyclic peptide , ring (chemistry) , combinatorial chemistry , ring closing metathesis , structural motif , hydrogen bond , peptide , metathesis , molecule , organic chemistry , biochemistry , in vitro , polymerization , polymer
Analogs of the natural product urukthapelstatin A that belongs to the rare family of polyazole cyclopeptides were synthesized and their cytotoxic activities were determined to gather data toward structure–activity relationships. Crucial steps within the convergent syntheses were a macrothiolactonization and a subsequent aza ‐Wittig reaction to install the heterocyclic backbone. The synthesis design was proven to be generally suitable for the formation of these azole containing cyclopeptides. Two analogs were structurally characterized by X‐ray crystallography which unveiled the planar assembly of the five catenated azoles as well as a unique hydrogen bond network. A conformational comparison to the known natural products was conducted. Cytotoxicity data showed the importance of key structural features with respect to the bioactivity including the phenyl ring attached to the eastern oxazole and the rigid, lipophilic tripeptide section.