Features of Phase Formation of Pyrochlore-type Ceramics Bi2Mg(Zn)1-x Ni x Ta2O9.

The phase formation of complex pyrochlores (space group Fd-3m) Bi2Mg(Zn)1-x Ni x Ta2O9 was investigated during solid-phase synthesis. It was found that the pyrochlore phase precursor in all cases was α-BiTaO4. The pyrochlore phase synthesis reaction proceeds mainly at temperatures above 850-900 °C and consists in the interaction of bismuth orthotantalate with a transition element oxide. The influence of magnesium and zinc on the course of pyrochlore synthesis was revealed. The reaction temperatures of magnesium and nickel (800 and 750 °C, respectively) were determined. The change in the pyrochlore unit cell parameter depending on the synthesis temperature was analyzed for both systems. Nickel-magnesium pyrochlores are characterized by a porous dendrite-like microstructure with a grain size of 0.5-1.0 microns, and the porosity of the samples reaches 20 percent. The calcination temperature does not significantly affect the microstructure of the samples. Prolonged calcination of the preparations leads to the coalescence of grains with the formation of larger particles. Nickel oxide has a sintering effect on ceramics. The studied nickel-zinc pyrochlores are characterized by a low-porous dense microstructure. The porosity of the samples does not exceed 10%. The optimal conditions for obtaining phase-pure pyrochlores (1050 °C and 15 h) were determined.

Pre-mRNA splicing-modulatory pharmacophores: the total synthesis of herboxidiene, a pladienolide-herboxidiene hybrid analog and related derivatives.

Herboxidiene is a natural product that has previously been shown to exhibit antitumor activity by targeting the spliceosome. This activity makes herboxidiene a valuable starting point for the development of anticancer drugs. Here, we report an improved enantioselective synthesis of herboxidiene and the first report of its biologically active totally synthetic analog: 6-norherboxidiene. The synthesis of the tetrahydropyran moiety utilizes the novel application of inverse electron-demand Diels-Alder chemistry and the Ferrier-type rearrangement as key steps. We report, for the first time, cytotoxicity IC50s for synthetic herboxidiene and analogs in human tumor cell lines. We have also demonstrated that synthetic herboxidiene and its analogs can potently modulate the alternate splicing of MDM-2 pre-mRNA.

Discovery, synthesis, and biological evaluation of a novel group of selective inhibitors of filoviral entry.

Herein, we report the development of an antifiloviral screening system, based on a pseudotyping strategy, and its application in the discovery of a novel group of small molecules that selectively inhibit the Ebola and Marburg glycoprotein (GP)-mediated infection of human cells. Using Ebola Zaire GP-pseudotyped HIV particles bearing a luciferase reporter gene and 293T cells, a library of 237 small molecules was screened for inhibition of GP-mediated viral entry. From this assay, lead compound 8a was identified as a selective inhibitor of filoviral entry with an IC(50) of 30 µM. To analyze functional group requirements for efficacy, a structure-activity relationship analysis of this 3,5-disubstituted isoxazole was then conducted with 56 isoxazole and triazole derivatives prepared using "click" chemistry. This study revealed that while the isoxazole ring can be replaced by a triazole system, the 5-(diethylamino)acetamido substituent found in 8a is required for inhibition of viral-cell entry. Variation of the 3-aryl substituent provided a number of more potent antiviral agents with IC(50) values ranging to 2.5 µM. Lead compound 8a and three of its derivatives were also found to block the Marburg glycoprotein (GP)-mediated infection of human cells.

Reduction of solid-supported olefins and alkynes.

The reduction of carbon-carbon multiple bonds in alkynes and olefins supported on a polystyrene resin has been investigated. Homogeneous catalysis by titanocene reagents is effective for the stereoselective preparation of cis-olefins from diarylacetylenes, while the use of copper(I) hydride reagents is effective for the reduction of alpha,beta-unsaturated ketones.