Palladium-catalyzed denitrogenation reaction of 1,2,3-benzotriazin-4(3H)-ones incorporating isocyanides

1,2,3-Benzotriazin-4(3H)-ones and 1,2,3,4-benzothiatriazine 1,1(2H)-dioxide reacted with isocyanides in the presence of a palladium catalyst to give 3-(imino)isoindolin-1-ones and 3-(imino)thiaisoindoline 1,1-dioxides, respectively, in high yield. An intermediate azapalladacycle was generated through denitrogenation of the triazine moiety, and an isocyanide was incorporated therein.     

Copper-catalyzed direct sulfoximination of azoles and polyfluoroarenes under ambient conditions

The direct dehydrogenative C-N coupling of azoles or polyfluoroarenes with N-H sulfoximines proceeds effectively in the presence of a copper catalyst at room temperature under air to afford the corresponding N-arylsulfoximines in good to high yields.     

Influence of particle design on oral absorption of poorly water-soluble drug in a silica particle-supercritical fluid system

The physicochemical characteristics and oral absorption of a poorly water-soluble drug, K-832, adsorbed onto porous silica (Sylysia 350), were compared with those of K-832 adsorbed onto non-porous silica (Aerosil 200). K-832 and silica were treated with supercritical CO(2) (scCO(2)) to produce K-832-Sylysia 350 and K-832-Aerosil 200 formulations. Scanning electron microscopy, polarizing microscopy, powder X-ray diffraction, and differential scanning calorimetry results suggested that K-832 mainly existed in an amorphous state in both formulations. The specific surface area of both formulations was much larger than that of pure K-832 crystals. The dissolution rate of K-832 from both formulations was considerably greater than that from corresponding physical mixtures due to rapid wetting of the hydrophilic carrier surfaces and amorphous state, the dissolution from the K-832-Sylysia 350 formulation being the fastest. In vivo absorption tests on the two formulations indicated no significant differences in their peak concentration (C(max)) and the area under their plasma concentration-time curve (AUC), while the concentrations of K-832 in the K-832-Sylysia 350 formulation were significantly higher than those in the K-832-Aerosil 200 formulation 1 h and 1.5 h after administration of these formulations (p<0.05). This could be attributed to the different dispersion states of K-832 in the formulations due to their different three-dimensional structures (porous and non-porous). In physical stability tests, the amorphous drugs in both formulations were stable at room temperature for at least 14 months. Thus, the absorption of poorly water-soluble drugs could be greatly improved by adsorption onto porous silica using scCO(2).     

Stereochemically controlled asymmetric 1,2-reduction of enones mediated by a chiral sulfoxide moiety and a lanthanum(III) ion

Enantiomerically pure (Z)-β-sulfinyl allylic alcohols of either handedness can be readily prepared from (Z)-β-sulfinyl enones using NaBH(4) or DIBAL reductants in the presence of LaCl(3) as a chelating agent. A chiral sulfoxide auxiliary induces the remote 1,2-asymmetric reduction (1,4-induction) to afford various chiral allylic alcohols in high yields with excellent stereoselectivities (up to 100% de).     

Cloning and sequence analysis of the poly(3-hydroxyalkanoic acid)-synthesis genes ofPseudomonas acidophila

Pseudomonas acidophila can grow with CO₂ as a sole carbon source by the possession of a recombinant plasmid that clones genes that confer chemolithoautotrophic growth ability derived from the H₂-oxidizing bacteriumAlcaligenes hydrogenophilus. H₂-oxidizing bacteria produce poly(3-hydroxybutyric acid) (PHB) from CO₂, but recombinant P.acidophila can produce the more useful biopolymer poly(3-hydroxyalkanoic acid) (PHA). In this study, thepha genes ofP. acidophila were cloned and a sequence analysis was carried out. A gene library was constructed using the cosmid vector pVK102. A recombinant cosmid carrying thepha genes was selected by the complementation of a PHB-negative mutant ofAlcaligenes eutrophus H16. The resulting recombinant cosmid pIK7 contained a 14.8-kb DNA insert. Subcloning was done, and the recombinant plasmid pEH74 was selected by hybridization with theA. eutrophus H16pha genes.Escherichia coli possessing pEH74 produced PHB, indicating that pEH74 contained thepha genes ofP. acidophila. The nucleotide sequences of the PHA-synthesis genesphaA (3-ketothiolase),phaB (acetoacetyl-CoA reductase), andphaC (PHA synthase) in pEH74 were determined. The homologies ofphaA, phaB, andphaC betweenP. acidophila andA. eutrophus H16 were 64.7, 76.1, and 56.6%, respectively.

     

Direct extraction of the isovector deformation parameter β(1)2 from the (p,n) reaction of 56Fe

The reaction ⁵⁶Fe(p, n)⁵⁶Co leading to the analog of the ground state and the first excited 2⁺ state of ⁵⁶Fe has been studied at E_p=20, 28, 32 and35MeV. The direct process dominates at higher energies, thus the direct extraction of the isovector deformation parameter β⁽¹⁾₂ is feasible. It is found that β⁽¹⁾₂ is about three times larger than β⁽⁰⁾₂, the isoscalar deformation parameter.