205380-30-9Relevant articles and documents
Titanium Tetrachloride-Mediated Approach to Access 2-Chloro-2-Substituted Isoindolin-1-ones through the Addition of Alkynes to Acyliminium ions
Chen, Zhao-Dan,Guo, Jia-Ming,Si, Chang-Mei,Wei, Bang-Guo,Xu, Wen-Ke
, p. 2625 - 2633 (2021)
An asymmetric approach to access 2-substituted isoindolin-1-ones 9–11 was developed through TiCl4-mediated addition-chlorination of N,O-acetals 7 a–7 c with terminal alkynes 8. A range of substrates were amenable to this transformation, and the desired substituted isoindolin-1-ones were obtained in moderate to good yields with moderate diastereoselectivities.
X-ray crystal structures of Enterococcus faecalis thymidylate synthase with folate binding site inhibitors
Catalano, Alessia,Luciani, Rosaria,Carocci, Alessia,Cortesi, Debora,Pozzi, Cecilia,Borsari, Chiara,Ferrari, Stefania,Mangani, Stefano
, p. 649 - 664 (2016/08/12)
Infections caused by Enterococcus faecalis (Ef) represent nowadays a relevant health problem. We selected Thymidylate synthase (TS) from this organism as a potential specific target for antibacterial therapy. We have previously demonstrated that species-specific inhibition of the protein can be achieved despite the relatively high structural similarity among bacterial TSs and human TS. We had previously obtained the EfTS crystal structure of the protein in complex with the metabolite 5-formyl-tetrahydrofolate (5-FTHF) suggesting the protein role as metabolite reservoir; however, protein–inhibitors complexes were still missing. In the present work we identified some inhibitors bearing the phthalimidic core from our in-house library and we performed crystallographic screening towards EfTS. We obtained two X-ray crystallographic structures: the first with a weak phthalimidic inhibitor bound in one subunit and 5-hydroxymethylene-6-hydrofolic acid (5-HMHF) in the other subunit; a second X-ray structure complex with methotrexate. The structural information achieved confirm the role of EfTS as an enzyme involved in the folate pool system and provide a structural basis for structure-based drug design.
Multimetallic iridium-tin (Ir-Sn3) catalyst in N-acyliminium ion chemistry: Synthesis of 3-substituted isoindolinones via intra- and intermolecular amidoalkylation reaction
Maity, Arnab Kumar,Roy, Sujit
, p. 2627 - 2642 (2014/09/30)
The multimetallic iridium-tritin (Ir-Sn3) complex [Cp*Ir(SnCl3)2{SnCl2(H2O) 2}] (1) proved to be a highly effective catalyst towards C-OH bond activation of γ-hydroxylactams, leading to a nucleophilic substitution reaction known as the α-amidoalkylation reaction. Catalyst 1 can be easily synthesized from the reaction of (pentamethylcyclocyclopentadienyl)iridium dichloride dimer {[Cp*IrCl2]2} and tin(II) dichloride (SnCl2). In terms of catalyst loading, reaction conditions and yields of the product formed, 1 is found to be superior compared to classical Lewis acid catalysts. Different carbon (arenes, heteroarenes, allyltrimethylsilane, 1,3-dicarbonyls) and heteroatom (alcohols, thiols, amides and sulfonamides) nucleophiles have been successfully employed in the intramolecular and intermolecular alkylations, as well as in heterocyclization reactions. In the majority of cases good to excellent yields of 3-substituted isoindolinones and 5-substituted pyrrolidin-2-ones have been obtained. Besides, the reactions are also atom economical and salt free. It is proposed that the multimetallic Ir-Sn3 catalyst behaves as a mild and selective Lewis acid to activate the γ-hydroxylactam towards the formation of the N-acyliminium ion; the latter being trapped by potent nucleophiles leading to the desired products.
