Liquid-Phase Partial Hydrogenation of Phenylacetylene at Ambient Conditions Catalyzed by Pd-Fe-O Nanoparticles Supported on Silica.

Catalysts with no hazardous or toxic components are required for the selective hydrogenation of acetylenic bonds in the synthesis of pharmaceuticals, vitamins, nutraceuticals, and fragrances. The present work demonstrates that a high selectivity to alkene can be reached over a Pd-Fe-O/SiO2 system prepared by the co-impregnation of a silica support with a solution of the metal precursors (NH4)3[Fe(C2O4)3] and [Pd(NH3)4]Cl2 followed by thermal treatment in hydrogen or in air at 400 °C. A DRIFT spectroscopic study of CO adsorption revealed large shifts in the position of the Pdn+-CO bands for this system, indicating the strong effect of Fen+ on the Pd electronic state, resulting in a decreased rate of double C=C bond hydrogenation and an increased selectivity of alkyne hydrogenation to alkene. The prepared catalysts consisted of mono- and bimetallic nanoparticles on an SiO2 carrier and exhibited a selectivity as high as that of the commonly used Lindlar catalyst (which contains such hazardous components as lead and barium), while the activity of the Fe-Pd-O/SiO2 catalyst was an order of magnitude higher. The hydrogenation of a triple bond over the proposed Pd-Fe catalyst opens the way to selective hydrogenation over nontoxic catalysts with a high yield and productivity. Taking into account a simple procedure of catalyst preparation, this direction provides a rationale for the large-scale implementation of these catalysts.

Facile Synthesis of Micro-Mesoporous Copper Phyllosilicate Supported on a Commercial Carrier and Its Application for Catalytic Hydrogenation of Nitro-Group in Trinitrobenzene.

Development of novel Cu-based catalysts has become one of the frontiers in the catalytic production of platform chemicals and in environment protection. However, the known methods of their synthesis are too complicated and result in materials that cannot be used instantly as commercial catalysts. In the present work, a novel material has been synthesized by the facile method of deposition-precipitation using thermal hydrolysis of urea. The conditions for Cu phyllosilicate formation have been revealed (molar ratio urea:copper = 10, 92 °C, 8-11 h). The prepared Cu-based materials were studied by TG-DTA, SEM, TEM, XRD, N2 adsorption and TPR-H2 methods, and it was found that the material involves nanoparticles of micro-mesoporous copper phyllosilicate phase with a chrysocolla-like structure inside the pores of a commercial meso-macroporous silica carrier. The chrysocolla-like phase is first shown to be catalytically active in the selective reduction of the nitro-group in trinitrobenzene to an amino-group with molecular hydrogen. Complete conversion of trinitrobenzene with a high yield of amines has been achieved in short time under relatively mild conditions (170 °C, 1.3 MPa) of nitroarene hydrogenation over a copper catalyst.

Design, Synthesis and Biological Evaluation of Neogliptin, a Novel 2-Azabicyclo[2.2.1]heptane-Based Inhibitor of Dipeptidyl Peptidase-4 (DPP-4).

Compounds that contain (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid substituted with bicyclic amino moiety (2-aza-bicyclo[2.2.1]heptane) were designed using molecular modelling methods, synthesised, and found to be potent DPP-4 (dipeptidyl peptidase-4) inhibitors. Compound 12a (IC50 = 16.8 ± 2.2 nM), named neogliptin, is a more potent DPP-4 inhibitor than vildagliptin and sitagliptin. Neogliptin interacts with key DPP-4 residues in the active site and has pharmacophore parameters similar to vildagliptin and sitagliptin. It was found to have a low cardiotoxic effect compared to sitagliptin, and it is superior to vildagliptin in terms of ADME properties. Moreover, compound 12a is stable in aqueous solutions due to its low intramolecular cyclisation potential. These findings suggest that compound 12a has unique properties and can act as a template for further type 2 diabetes mellitus drug development.

Pd-Fe nanoparticles stabilized by chitosan derivatives for perchloroethene dechlorination.

A series of chitosan-stabilized Pd-NZVI (nano-zero-valent-iron) catalysts for dechlorination with variation in their composition and in the nature of the polymer has been prepared. The synthesis procedures and palladium and chitosan contents were optimized. It was demonstrated by the XPS method that Fe and Pd in Fe-Pd/chitosan samples exist in the metallic state. The positive shift of the binding energy as compared with the bulk metal shows that the iron metal in the surface layers exists as very small nanoparticles. The prepared materials were characterized also by the XAS method. The presence of O and N atoms in the first coordination shell of the central Fe atom in the Fe-Pd/chitosan samples certifies the binding of the Fe metal particles with the chitosan surface via OH and NH(2) groups. The samples are characterized by the high stability of the nanoparticles as compared to unstabilized Pd-NZVI. The materials were tested to evaluate their catalytic activity in the perchloroethene (PCE) dechlorination reaction. Some samples of chitosan-stabilized Pd-NZVI revealed a good performance in PCE degradation as compared to unstabilized Pd-NZVI.

Heterobiaryl human immunodeficiency virus entry inhibitors.

Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC(50) values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of 1 against a panel of clinical viral isolates. Moreover, current structure-activity relationship studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design.

Design and synthesis of human immunodeficiency virus entry inhibitors: sulfonamide as an isostere for the alpha-ketoamide group.

The crystal structures of many tertiary alpha-ketoamides reveal an orthogonal arrangement of the two carbonyl groups. Based on the hypothesis that the alpha-ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to its gp120 target via a similar conformation, we designed and synthesized a series of analogs in which the ketoamide group is replaced by an isosteric sulfonamide group. The most potent of these analogs, 14i, demonstrated antiviral potency comparable to 26 in the M33 pseudotyped antiviral assay. Flexible overlay calculations of a ketoamide inhibitor with a sulfonamide inhibitor revealed a single conformation of each that gave significantly better overlap of key pharmacophore features than other conformations and thus suggest a possible binding conformation for each class.