17145-91-4Relevant articles and documents
Design, Synthesis, and Biological Evaluation of Novel Pyrimido[4,5-b]indole Derivatives against Gram-Negative Multidrug-Resistant Pathogens
Kong, Qidi,Pan, Wei,Xu, Heng,Xue, Yaru,Guo, Bin,Meng, Xin,Luo, Cheng,Wang, Ting,Zhang, Shuhua,Yang, Yushe
supporting information, p. 8644 - 8665 (2021/06/28)
Due to the poor permeability across Gram-negative bacterial membranes and the troublesome bacterial efflux mechanism, only a few GyrB/ParE inhibitors with potent activity against Gram-negative pathogens have been reported. Among them, pyrimido[4,5-b]indol
Palladium-Catalyzed Long-Range Deconjugative Isomerization of Highly Substituted α,β-Unsaturated Carbonyl Compounds
Lin, Luqing,Romano, Ciro,Mazet, Clément
supporting information, p. 10344 - 10350 (2016/08/31)
The long-range deconjugative isomerization of a broad range of α,β-unsaturated amides, esters, and ketones by an in situ generated palladium hydride catalyst is described. This redox-economical process is triggered by a hydrometalation event and is thermodynamically driven by the refunctionalization of a primary or a secondary alcohol into an aldehyde or a ketone. Di-, tri-, and tetrasubstituted carbon-carbon double bonds react with similar efficiency; the system is tolerant toward a variety of functional groups, and olefin migration can be sustained over 30 carbon atoms. The refunctionalized products are usually isolated in good to excellent yield. Mechanistic investigations are in support of a chain-walking process consisting of repeated migratory insertions and β-H eliminations. The bidirectionality of the isomerization reaction was established by isotopic labeling experiments using a substrate with a double bond isolated from both terminal functions. The palladium hydride was also found to be directly involved in the product-forming tautomerization step. The ambiphilic character of the in situ generated [Pd-H] was demonstrated using isomeric trisubstituted α,β-unsaturated esters. Finally, the high levels of enantioselectivity obtained in the isomerization of a small set of α-substituted α,β-unsaturated ketones augur well for the successful development of an enantioselective version of this unconventional isomerization.
Rational Design, Synthesis, and Preliminary Structure-Activity Relationships of α-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella typhimurium O-Acetylserine Sulfhydrylase
Pieroni, Marco,Annunziato, Giannamaria,Beato, Claudia,Wouters, Randy,Benoni, Roberto,Campanini, Barbara,Pertinhez, Thelma A.,Bettati, Stefano,Mozzarelli, Andrea,Costantino, Gabriele
, p. 2567 - 2578 (2016/04/10)
Cysteine is a building block for several biomolecules that are crucial for living organisms. The last step of cysteine biosynthesis is catalyzed by O-acetylserine sulfydrylase (OASS), a highly conserved pyridoxal 5′-phosphate (PLP)-dependent enzyme, present in different isoforms in bacteria, plants, and nematodes, but absent in mammals. Beside the biosynthesis of cysteine, OASS exerts a series of moonlighting activities in bacteria, such as transcriptional regulation, contact-dependent growth inhibition, swarming motility, and induction of antibiotic resistance. Therefore, the discovery of molecules capable of inhibiting OASS would be a valuable tool to unravel how this protein affects the physiology of unicellular organisms. As a continuation of our efforts toward the synthesis of OASS inhibitors, in this work we have used a combination of computational and spectroscopic approaches to rationally design, synthesize, and test a series of substituted 2-phenylcyclopropane carboxylic acids that bind to the two S. typhymurium OASS isoforms at nanomolar concentrations.
