J. Appl. Cryst.の発刊に際して

Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ Alexander E. Sorochinsky, Santos Fustero,*,‡,§ Vadim A. Soloshonok,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andreś Estelleś, 46100 Burjassot, Valencia, Spain Laboratorio de Molećulas Orgańicas, Centro de Investigacioń Príncipe Felipe, C/ Eduardo Primo Yuf́era 3, 46012 Valencia, Spain Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastian, Spain IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv-94, Ukraine

Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).

The biaryl structural motif is a predominant feature in many pharmaceutically relevant and biologically active compounds. As a result, for over a century 1 organic chemists have sought to develop new and more efficient aryl -aryl bond-forming methods. Although there exist a variety of routes for the construction of aryl -aryl bonds, arguably the most common method is through the use of transition-metalmediated reactions. 2-4 While earlier reports focused on the use of stoichiometric quantities of a transition metal to carry out the desired transformation, modern methods of transitionmetal-catalyzed aryl -aryl coupling have focused on the development of high-yielding reactions achieved with excellent selectivity and high functional group tolerance under mild reaction conditions. Typically, these reactions involve either the coupling of an aryl halide or pseudohalide with an organometallic reagent (Scheme 1), or the homocoupling of two aryl halides or two organometallic reagents. Although a number of improvements have developed the former process into an industrially very useful and attractive method for the construction of aryl -aryl bonds, the need still exists for more efficient routes whereby the same outcome is accomplished, but with reduced waste and in fewer steps. In particular, the obligation to use coupling partners that are both activated is wasteful since it necessitates the installation and then subsequent disposal of stoichiometric activating agents. Furthermore, preparation of preactivated aryl substrates often requires several steps, which in itself can be a time-consuming and economically inefficient process.

http://aether.cmi.ua.ac.be/artikels/Artikels%20Gitte/Artikels/Reviews/Heck-Type-lautens.pdf

Aryl-aryl bond formation by transition-metal-catalyzed direct arylation.

■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

Recent applications of the Suzuki–Miyaura cross-coupling reaction in organic synthesis

We report that 1-(2-picolyl)-1,2,3-triazole (click triazole) forms stable complexes with transition-metal ions in which the coordination involves the triazole N2 nitrogen atom and the pendant 2-picolyl group. This is exemplified by model compound 1-(2-picolyl)-4-phenyl-1H-1,2,3-triazole (Lx) and its complexes with transition-metal ions of PtII, PdII, CuII, RuII, and AgI. The coordination was investigated experimentally and theoretically. Ligand Lx easily reacted at room temperature with cis-[PtCl2(DMSO)2], [Pd(CH3CN)4](BF4)2, CuCl2, [RuCl(μ-Cl)(η6-p-cymene)]2, and AgNO3 to give stable chelates [PtCl2Lx] (1), [Pd(Lx)2](BF4)2 (2), [CuCl2(Lx)2] (3), [RuCl(η6-p-cymene)Lx]OTf (4), and [Ag2(Lx)2(NO3)2] (5), respectively, in 60−98% yield. The structures of 1−5 were unambiguously confirmed by NMR spectroscopy and single-crystal X-ray diffraction analysis. Density functional theory calculations were carried out in order to theoretically investigate the stabilization factors in 1−5. A comparison of the chelating pr...

Click-triazole N2 coordination to transition-metal ions is assisted by a pendant pyridine substituent.

X-Ray crystallographic, NMR and antimicrobial activity studies of magnesium complexes of fluoroquinolones - racemic ofloxacin and its S-form, levofloxacin

The 1,4-disubstituted 1,2,3-triazole ligand prepared by click chemistry 1-(2-picolyl)-4-phenyl-1H-1,2,3-triazole (ppt) was investigated as novel chelating ligand for Ru(II) complexes with potential antitumor activity. The preparation and structural characterization, mainly by NMR spectroscopy in solution and by X-Ray crystallography in the solid state, of four new Ru(II) complexes is reported: two isomeric Ru-dmso compounds, trans,cis-[RuCl2(dmso-S)2(ppt)] (1) and cis,cis-[RuCl2(dmso-S)2(ppt)] (2), and two half-sandwich Ru-[9]aneS3 coordination compounds, [Ru([9]aneS3)(dmso-S)(ppt)][CF3SO3]2 (3) and [Ru([9]aneS3)Cl(ppt)][CF3SO3] (4). In all compounds ppt firmly binds to ruthenium in a bidentate fashion through the pyridyl nitrogen atom and the triazole N2, thus forming a puckered six-membered ring. The chemical behavior in aqueous solution of the water-soluble complexes 3 and 4 was studied by UV-Vis and NMR spectroscopy and compared to that of the previously described organometallic analogue [Ru(η6-p-cymene)Cl(ppt)][Cl] (5) in view of their potential antitumor activity. Compounds 3–5 were tested also in vitro for cytotoxic activity against two human cancer cell lines, one sensitive and one resistant to cisplatin, in comparison with cisplatin. Compound 4, the one that aquates faster, was found to be more cytotoxic than cisplatin against human lung squamose carcinoma cell line (A-549).

/pdf/1-2-picolyl-substituted-1-2-3-triazole-as-novel-chelating-25ljblii3b.pdf

1-(2-Picolyl)-substituted 1,2,3-triazole as novel chelating ligand for the preparation of ruthenium complexes with potential anticancer activity

Cp*-Ir(III) complexes with additional chelating ligands are known active pre-catalysts for the oxygenation of C–H bonds. We present here eight examples of such complexes where the denticity of the chelating ligands has been varied from the well-known 2,2′-bpy through pyridyl-triazole, bi-triazole to ligands containing pyridyl-triazolylidene, triazolyl-triazolylidene and bi-triazolylidenes. Additionally, we also compare the catalytic results to complexes containing chelating cyclometallated ligands with additional triazole or triazolylidene donors. Single crystal X-ray structural data are presented for all the new complexes that contain one or more triazolylidene donors of the mesoionic carbene type. We present the first example of a metal complex containing a chelating triazole-triazolylidene ligand. The results of the catalytic screening show that complexes containing unsymmetrical donors of the pyridyl-triazole or pyridyl-triazolylidene types are the most potent pre-catalysts for the C–H oxygenation of cyclooctane in the presence of either m-CPBA or NaIO4 as a sacrificial oxidant. These pre-catalysts can also be used to oxygenate C–H bonds in other substrates such as fluorene and ethyl benzene. The most potent pre-catalysts presented here work with a lower catalyst loading and under milder conditions while delivering better product yields in comparison with related literature known Ir(III) pre-catalysts. These results thus point to the potential of ligands with unsymmetrical donors obtained through the click reaction in oxidation catalysis.

/pdf/catalytic-oxygenation-of-sp3-c-h-bonds-with-ir-iii-complexes-3wfgq16ffl.pdf

Catalytic oxygenation of sp3 “C–H” bonds with Ir(III) complexes of chelating triazoles and mesoionic carbenes

The seminal contributions by Sonogashira, Cassar and Heck in mid 1970s on Pd/Cu- and Pd-catalysed (copper-free) coupling of acetylenes with aryl or vinyl halides have evolved in myriad applications. Despite the enormous success both in academia and in industry, however, critical mechanistic questions of this cross-coupling process remain unresolved. In this study, experimental evidence and computational support is provided for the mechanism of copper-free Sonogashira cross-coupling reaction. In contrast to the consensus monometallic mechanism, the revealed pathway proceeds through a tandem Pd/Pd cycle linked via a multistep transmetallation process. This cycle is virtually identical to the Pd/Cu tandem mechanism of copper co-catalysed Sonogashira cross-couplings, but the role of CuI is played by a set of PdII species. Phosphine dissociation from the square-planar reactants to form transient three-coordinate Pd species initiates transmetallation and represents the rate-determining step of the process.

/pdf/mechanism-of-copper-free-sonogashira-reaction-operates-5rltmmt3ns.pdf

Janez Košmrlj

Papers

Click-triazole N2 coordination to transition-metal ions is assisted by a pendant pyridine substituent.

X-Ray crystallographic, NMR and antimicrobial activity studies of magnesium complexes of fluoroquinolones - racemic ofloxacin and its S-form, levofloxacin

1-(2-Picolyl)-substituted 1,2,3-triazole as novel chelating ligand for the preparation of ruthenium complexes with potential anticancer activity

Catalytic oxygenation of sp3 “C–H” bonds with Ir(III) complexes of chelating triazoles and mesoionic carbenes

Mechanism of copper-free Sonogashira reaction operates through palladium-palladium transmetallation