929642-48-8Relevant articles and documents
Design, Synthesis, and Properties of a Potent Inhibitor of Pseudomonas aeruginosa Deacetylase LpxC
Piizzi, Grazia,Parker, David T.,Peng, Yunshan,Dobler, Markus,Patnaik, Anup,Wattanasin, Som,Liu, Eugene,Lenoir, Francois,Nunez, Jill,Kerrigan, John,McKenney, David,Osborne, Colin,Yu, Donghui,Lanieri, Leanne,Bojkovic, Jade,Dzink-Fox, Joann,Lilly, Maria-Dawn,Sprague, Elizabeth R.,Lu, Yipin,Wang, Hongming,Ranjitkar, Srijan,Xie, Lili,Wang, Bing,Glick, Meir,Hamann, Lawrence G.,Tommasi, Ruben,Yang, Xia,Dean, Charles R.
, p. 5002 - 5014 (2017/06/28)
Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-Acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo.
Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics
Wünsch, Matthias,Schr?der, David,Fr?hr, Tanja,Teichmann, Lisa,Hedwig, Sebastian,Janson, Nils,Belu, Clara,Simon, Jasmin,Heidemeyer, Shari,Holtkamp, Philipp,Rudlof, Jens,Klemme, Lennard,Hinzmann, Alessa,Neumann, Beate,Stammler, Hans-Georg,Sewald, Norbert
supporting information, p. 2428 - 2441 (2017/12/06)
The amide moiety of peptides can be replaced for example by a triazole moiety, which is considered to be bioisosteric. Therefore, the carbonyl moiety of an amino acid has to be replaced by an alkyne in order to provide a precursor of such peptidomimetics. As most amino acids have a chiral center at Cα, such amide bond surrogates need a chiral moiety. Here the asymmetric synthesis of a set of 24 N-sulfinyl propargylamines is presented. The condensation of various aldehydes with Ellman's chiral sulfinamide provides chiral N-sulfinylimines, which were reacted with (trimethylsilyl)ethynyllithium to afford diastereomerically pure N-sulfinyl propargylamines. Diverse functional groups present in the propargylic position resemble the side chain present at the Cα of amino acids. Whereas propargylamines with (cyclo)alkyl substituents can be prepared in a direct manner, residues with polar functional groups require suitable protective groups. The presence of particular functional groups in the side chain in some cases leads to remarkable side reactions of the alkyne moiety. Thus, electron-withdrawing substituents in the Cα-position facilitate a base induced rearrangement to α,β-unsaturated imines, while azide-substituted propargylamines form triazoles under surprisingly mild conditions. A panel of propargylamines bearing fluoro or chloro substituents, polar functional groups, or basic and acidic functional groups is accessible for the use as precursors of peptidomimetics.
Asymmetric syntheses of 1-Aryl-2,2,2-trifluoroethylamines via diastereoselective 1,2-addition of arylmetals to 2-Methyl-N-(2,2,2- trifluoroethylidene)propane-2-sulfinamide
Truong, Vouy Linh,Menard, Madeleine S.,Dion, Isabelle
, p. 683 - 685 (2007/10/03)
Condensation of N-tert-butanesulfinamide (S)-1 with trifluoroacetaldehyde hydrate 2a afforded 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide 3. Without isolation and purification, imine 3 was added to various aryllithium reagents to give high
