555-59-9Relevant articles and documents
Dichloro Butenediamides as Irreversible Site-Selective Protein Conjugation Reagent
Abegg, Daniel,Adibekian, Alexander,Afonso, Cláudia F.,Bernardes, Gon?alo J. L.,Corzana, Francisco,Laserna, Victor,Martin, Esther M.,Ravn, Peter
supporting information, p. 23750 - 23755 (2021/10/01)
We describe maleic-acid derivatives as robust cysteine-selective reagents for protein labelling with comparable kinetics and superior stability relative to maleimides. Diamide and amido-ester derivatives proved to be efficient protein-labelling species with a common mechanism in which a spontaneous cyclization occurs upon addition to cysteine. Introduction of chlorine atoms in their structures triggers ring hydrolysis or further conjugation with adjacent residues, which results in conjugates that are completely resistant to retro-Michael reactions in the presence of biological thiols and human plasma. By controlling the microenvironment of the reactive site, we can control selectivity towards the hydrolytic pathway, forming homogeneous conjugates. The method is applicable to several scaffolds and enables conjugation of different payloads. The synthetic accessibility of these reagents and the mild conditions required for fast and complete conjugation together with the superior stability of the conjugates make this strategy an important alternative to maleimides in bioconjugation.
Synthesis of Tetrahydroisoindolinones via a Metal-Free Dehydrogenative Diels-Alder Reaction
Xu, Wen-Lei,Tang, Lei,Ge, Chen-Yu,Chen, Jie,Zhou, Ling
supporting information, p. 2268 - 2273 (2019/04/10)
A metal-free dehydrogenative Diels-Alder reaction of substituted alkenes for the synthesis of tetrahydroisoindolinones has been exploited for the first time. This new method features functional group tolerance and broad substrate scope, providing an efficient access to biologically active tetrahydroisoindolinone skeletons with endo steroselectivity in good to excellent yields. (Figure presented.).
Acetylcholinesterase inhibition by products generated in situ from the transformation of N-arylisomaleimides
Guevara, Juan A.,Trujillo, José G.,Quintana, Delia,Jiménez, Hugo A.,Arellano, Mónica G.,Bahena, José R.,Tamay, Feliciano,Ciprés, Fabiola J.
, p. 989 - 1003 (2017/12/18)
When N-arylisomaleimides were transformed under enzymatic reaction conditions, the transformation reaction proved to be influenced by electronic effects. This was demonstrated qualitatively by 1H NMR spectroscopy and quantitatively by monitoring the kinetic of isomerization of N-phenylisomaleimide to N-phenylmaleimide. Subsequently, the first pseudo-order and activation energy (Ea) of the process were determined. The compounds showed in situ influence on AChE inhibition. The derivatives with electron-withdrawing groups exhibited a better effect than those having electron-donating groups. The in silico experiments show that the ligands evaluated established interactions with the CAS site. This suggests that these compounds could be useful for generating better reversible and competitive inhibitors of AChE.
