42822-58-2Relevant academic research and scientific papers
σ2-P Ligands: Convenient syntheses of N-methyl-1,3- benzazaphospholes
Ghalib, Mohammed,Niaz, Basit,Heinicke, Joachim W.,Jones, Peter G.
, p. 5012 - 5014,3 (2012)
A convenient three-step route to 1,5-dimethyl-1,3-benzazaphosphole via Cu- or Pd-catalyzed phosphonylation of 2-iodo-4-methylaniline, reduction to 2-phosphino-4-methylaniline, and disproportionative cyclization with excess formaldehyde is reported. N-Methylbenzazaphospholes can be functionalized in the 2-position via α-CH-lithiation with tBuLi and are π-acidic σ2P-ligands.
Discovery of benzophosphadiazine drug candidate IDX375: A novel hepatitis C allosteric NS5B RdRp inhibitor
Paparin, Jean-Laurent,Amador, Agnès,Badaroux, Eric,Bot, Stéphanie,Caillet, Catherine,Convard, Thierry,Da Costa, Daniel,Dukhan, David,Griffe, Ludovic,Griffon, Jean-Fran?ois,LaColla, Massimiliano,Leroy, Frédéric,Liuzzi, Michel,Giulia Loi, Anna,McCarville, Joe,Mascia, Valeria,Milhau, Julien,Onidi, Loredana,Pierra, Claire,Rahali, Rachid,Rosinosky, Elodie,Sais, Efisio,Seifer, Maria,Surleraux, Dominique,Standring, David,Dousson, Cyril B.
, p. 2634 - 2640 (2017/05/10)
Hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells, and as a consequence is an attractive target for selective inhibition. This paper describes the discovery of a novel family of HCV NS5B non-nucleoside inhibitors inspired by the bioisosterism between sulfonamide and phosphonamide. Systematic structural optimization in this new series led to the identification of IDX375, a potent non-nucleoside inhibitor that is selective for genotypes 1a and 1b. The structure and binding domain of IDX375 were confirmed by X-ray co-crystalisation study.
METHODS AND COMPOSITIONS FOR THE REMOVAL OF ALDEHYDE ADDUCTS AND CROSSLINKS FROM BIOMOLECULES
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Page/Page column 52; 53, (2016/04/10)
Methods are provided for reducing the number of aldehyde adducts and/or crosslinks from fixed biomolecules. In some cases, subject methods include contacting a sample having aldehyde fixed biomolecules (e.g., a biological sample such as a formalin fixed p
Solvent-controlled lithiation of PC-N-heterocycles: Synthesis of mono- and bis(trimethylsilyl)-tert-butyl-dihydrobenzazaphospholes - A new type of highly bulky and basic phosphine ligands
Ghalib, Mohammed,Jones, Peter G.,Heinicke, Joachim W.
, p. 44 - 51 (2014/05/20)
The influence of solvents on the lithiation of N-methyl-1,3- benzazaphospholes is reported; these are accessible via catalytic phosphonylation of 2-bromoanilines, subsequent reduction to 2-phosphinoanilines and acid-catalysed disproportionative ring closure with excess paraformaldehyde. Reactions with tBuLi in polar solvents (THF, Et2O), particularly in the presence of tBuOK, lead to 2-lithiobenzazaphospholes (CH-lithiation) whereas hydrocarbons favour normal (hexane) or inverse (toluene) addition at the PC bond. Reactive Li-species were trapped by ClSiMe3, present during the lithiation in hydrocarbons, and give rise to 2- and 3-trimethylsilyl-dihydro-1,3-benzazaphospholes, respectively. In hexane, via preferred lithiation of the primary adduct, the 2,2′- bis(trimethylsilyl)-dihydro-1,3-benzazaphosphole is the main product. 5-Methyl-1,3-benzazaphosphole, with NH function, reacts in toluene in the normal mode to 3-tert-butyl-1,2-bis(trimethylsilyl)-5-methyl- dihydrobenzazaphosphole. The sterically demanding tert-butyl and trimethylsilyl groups are arranged in anti-position as shown by crystal structure analyses, the second 2-SiMe3 group in gauche position. The P-tert-butyl-2, 2′-bis(trimethylsilyl)-dihydrobenzazaphospholes represent a new type of sterically congested dialkylaryl phosphine ligands with increased basicity by the +I-effect of the silyl groups and +M-effect of the basic nitrogen in o-position.
Coplanar tetracyclic π-excess σ2P ligands
Niaz, Basit,Iftikhar, Fatima,Kindermann, Markus K.,Jones, Peter G.,Heinicke, Joachim
, p. 4220 - 4227 (2013/09/12)
The acid-catalyzed reactions of 5-methyl-2-phosphanylaniline (1) with dialdehydes were studied. Whereas the reaction with glyoxal provides a mixture of two 1H-1,3-benzazaphospholes, 2 and 3, by concomitant reduction of a CHO group and C-C bond cleavage, respectively, the reaction with o-phthalic dicarbaldehyde provided in excellent yield the tetracyclic planar benzazaphosphole 4, which was characterized by crystal structure analysis. The active hydrogen atoms, delivered by aromatization of a dihydrobenzazaphosphole intermediate, forms an N-CH2 bridge by reductive N-alkylation. Pyridine-2,6-dicarbaldehyde reacts analogously but not chemoselectively and, thus, gives two isomers 5 and 6. Condensation with pyridine-2,6-dicarbaldehyde afforded the bis(benzazaphosphole)pyridine pincer ligand 7, but along with 2-(benzazaphospholyl)-6-tolylpyridine (8) by partial P-C bond cleavage. The high upfield 31P NMR chemical shift of 4 compared to those of normal benzazaphospholes indicates it to be a particularly π-rich σ2P ligand. Aromatization-driven acid-catalyzed condensations of the N,P-diprimary compound 1 with dialdehydes are coupled with hydrogen transfer reactions. With glyoxal and pyridine-2,6-dicarbaldehyde this gives rise to side products, but with o-C6H4(CHO)2, high yields of 4 are obtained. π-Delocalization through the coplanar aryl rings causes high π-density at the phosphorus atom.
