203243-61-2Relevant articles and documents
Synthesis and protein degradation capacity of photoactivated enediynes
Fouad, Farid S.,Wright, Justin M.,Plourde II, Gary,Purohit, Ajay D.,Wyatt, Justin K.,El-Shafey, Ahmed,Hynd, George,Crasto, Curtis F.,Lin, Yiqing,Jones, Graham B.
, p. 9789 - 9797 (2007/10/03)
The viability of proteins as targets of thermally and photoactivated enediynes has been confirmed at the molecular level. Model studies using a labeled substrate confirmed the efficacy of atom transfer from diyl radicals produced from enediynes to form captodatively stabilized carbon centered aminoacyl radicals, which then undergo either fragmentation or dimerization. To exploit this finding, a family of enediynes was developed using an intramolecular coupling strategy. Derivatives were prepared and used to target specific proteins, showing good correlation between affinity and photoinduced protein degrading activity. The findings have potential applications in the design of artificial chemical proteases and add to our understanding of the mechanism of action of the clinically important enediyne antitumor antibiotics.
An iterative approach to cis-oligodiacetylenes
Kosinski, Christoph,Hirsch, Andreas,Heinemann, Frank W.,Hampel, Frank
, p. 3879 - 3890 (2007/10/03)
Phenyl-terminated cis-oligodiacetylenes such as 18, containing a π-conjugated backbone with four triple and three double bonds, were synthesized using Pd-catalysed Sonogashira coupling reactions. Compound 18 represents the longest cis-oligoenyne system to date, but it suffers from the drawback of cis/trans isomerization observed in solution. In order to avoid cis/trans isomerization in such cis-oligodicacetylenes, the ene moieties within the oligomeric backbone were locked by incorporation into ring systems. 1,2-Dibromocyclopentene was used as an olefinic building block for this purpose, permitting the iterative synthesis of the cis-oligodiacetylenes 27 and 28, possessing the same π-conjugated backbone as 18. Unlike that compound, however, 27 and 28 are stable both in solution and in the solid state. Whereas X-ray crystallography revealed a completely planar structure for 27 in the single crystal, NMR and computational investigations suggest that a preferred helical conformation is likely in solution.
