1070774-68-3

Upstream product

• 1458-98-6 2-methyl-3-bromo-1-propene 
• 223906-53-4 (4R)-N-Propionyl-5,5-diphenyl-4-isopropyloxazolidin-2-one 
• 191090-32-1 (R)-4-(1-methylethyl)-5,5-diphenyl-1,3-oxazolidin-2-one 

Relevant academic research and scientific papers

Thermal proteome profiling efficiently identifies ribosome destabilizing oxazolidinones

Identifying the targets of bioactive small molecules is a challenging endeavor for which no general solution currently exists. Classical affinity purification experiments suffer from the need to functionalise a bioactive compound and link it to a solid support, which may interfere with target binding. A modern mass spectrometry-based proteomics technique that has partially circumvented this problem is thermal proteome profiling (TPP), which determines the effect of an unmodified small molecule on the thermal stability of the whole proteome simultaneously. Here, we use TPP to identify the mode-of-action of a newly-discovered autophagy inhibitor based on oxazolidinones often employed as chiral auxiliaries. Surprisingly, a significant portion of all ribosomal proteins were found to be destabilized by the inhibitor, highlighting the utility of this technology for determining a challenging mode-of-action.

Synthesis and structure-activity correlation of natural-product inspired cyclodepsipeptides stabilizing F-actin

The fundamental role played by actin In the regulation of eukaryotic cell maintenance and motility renders it a primary target for small-molecule intervention. in this arena, a class of potent cytotoxic cyclodepsipeptide natural products has emerged over the last quarter-century to stimulate the fields of biology and chemistry with their unique actin-stabilizing properties and complex peptide-polyketide hybrid structures. Despite considerable research effort, a structural basis for the activity of these secondary metabolites remains elusive, not least for the lack of high-resolution structural data and a reliable synthetic route to diverse compound libraries. in response to this, an efficient solid-phase approach has been developed and successfully applied to the total synthesis of Jasplakinolide and chondramide C and diverse analogues. The key macrocylization step was realized using ruthenium-catalyzed ring-closing metathesis (RCM) that in the course of a library synthesis produced discernible trends in metathesis reactivity and E/Z-selectivity, After optimization, the RCM step could be operated under mild conditions, a result that promises to facilitate the synthesis of more extensive analogue libraries for structure-function studies. The growth inhibitory effects of the synthesized compounds were quantified and structure-activity correlations established which appear to be in good alignment with relevant biological data from natural products. in this way a number of potent unnatural and simplified analogues have been found. Furthermore, potentially important stereochemical and structural components of a common pharmacophore have been identified and rationalized using molecular modeling. These data will guide in-depth mode-of-action studies, especially into the relationship between the cytotoxicity of these compounds and their actin-perturbing properties, and should inform the future design of simplified and functionalized actln stabilizers as well.

Total synthesis of chondramide C and its binding mode to F-actin

(Chemical Equation Presented) Actin glue: An E-selective ring-closing metathesis as the key step allowed the solid-phase-based total synthesis of the F-actin stabilizer chondramide C as well as the establishment of its hitherto unknown stereochemistry. A strong influence of the polyketide configuration was revealed in cellular assays. Docking studies on the F-actin filament structure led to a detailed model of the binding site.