1227367-59-0Relevant academic research and scientific papers
Ynamide-Mediated Thiopeptide Synthesis
Yang, Jinhua,Wang, Changliu,Xu, Silin,Zhao, Junfeng
supporting information, p. 1382 - 1386 (2019/01/08)
Exploration of the full potential of thioamide substitution as a tool in the chemical biology of peptides and proteins has been hampered by insufficient synthetic strategies for the site-specific introduction of a thioamide bond into a peptide backbone. A novel ynamide-mediated two-step strategy for thiopeptide bond formation with readily available monothiocarboxylic acids as thioacyl donors is described. The α-thioacyloxyenamide intermediates formed from the ynamides and monothiocarboxylic acids can be purified, characterized, and stored. The balance between their activity and stability enables them to act as effective thioacylating reagents to afford thiopeptide bonds under mild reaction conditions. Amino acid functional groups such as OH, CONH2, and indole NH groups need not be protected during thiopeptide synthesis. The modular nature of this strategy enables the site-specific incorporation of a thioamide bond into peptide backbones in both solution and the solid phase.
Mapping of the Modular Closthioamide Architecture Reveals Crucial Motifs of Polythioamide Antibiotics
Kloss, Florian,Chiriac, Alina Iulia,Hertweck, Christian
supporting information, p. 15451 - 15458 (2016/02/18)
Closthioamide, the first known secondary metabolite from an anaerobic microorganism (Clostridium cellulolyticum), represents a highly potent antibiotic that is active against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE) at nanomolar concentrations. To unveil structure-activity relationships of the unusual polythioamide natural product we have designed a synthetic grid to access analogues with altered terminal aromatic moieties, diverse p-phenyl substituents, different types and sizes of aliphatic spacers, varying numbers of thioamide residues, and diverse sizes and symmetries of the poly-β-thioalanyl backbone. A library of 28 closthioamide analogues was tested against a panel of human pathogenic bacteria. We found that aromatic terminal groups, the defined length of the spacer groups, the presence of all six thioamide residues and the modular arrangement of the β-thioalanyl units play essential roles for the antibiotic activity of closthioamide, yet there is a degree of freedom in the symmetry of the molecule. This study yields the first insights into pivotal structural motifs and the structural space of this new family of antibiotics, a prerequisite for the development of these promising antibiotics. Widening the scope: Structural motifs of closthioamide, the first antibiotic from strictly anaerobic microorganisms, were dissected and altered to unveil residues that are pivotal for antimicrobial activity. Using a modular approach, a library of 28 analogues was synthesized. First insights were gained into the structural space of this new family of antibiotics (see diagram).
CLOSTHIOAMIDES
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, (2011/05/11)
This invention relates to the field of biologically active compounds and specifically to closthioamides, pharmaceutical compositions comprising these compounds, and their use as antibiotic, antifungal, and/or cytotoxic agent.
Highly efficient total synthesis of the clostridium-derived anti-MRSA antibiotic closthioamide
Kloss, Florian,Lincke, Thorger,Hertweck, Christian
, p. 1429 - 1431 (2011/04/25)
The antibiotic closthioamide from Clostridium cellulolyticum, the first example of a secondary metabolite from strictly anaerobic bacteria, was synthesized by a versatile and highly efficient synthetic route. This starts from simple building blocks and involves convergent peptide coupling and polythionation. The antibiotic closthioamide from Clostridium cellulolyticum, the first example of a secondary metabolite from strictly anaerobic bacteria, was synthesized by a versatile and highly efficient route starting from simple building blocks, involving convergent peptide coupling and polythionation. Copyright
