Highly enantioselective synthesis of chiral 3-substituted indolines by catalytic asymmetric hydrogenation of indoles

[reaction: see text] N-Tosyl 3-substituted indoles were hydrogenated with high enantioselectivities (95-98% ee) by use of a trans-chelating chiral bisphosphine, (S,S)-(R,R)-PhTRAP ligand. The chiral catalyst, which was generated in situ from [Rh(nbd)(2)]SbF(6), PhTRAP, and Cs(2)CO(3), is useful for enantioselectively synthesizing a range of diverse optically active indolines possessing a chiral carbon at the 3-position.     

Synthesis and evaluation of novel pyrimido-acridone, -phenoxadine, and -carbazole as topoisomerase II inhibitors

As part of a series of studies to discover new topoisomerase II inhibitors, novel pyrimidoacridones, pyrimidophenoxadines, and pyrimidocarbazoles were synthesized, and in vitro and in vivo antitumor activities and DNA-protein and/or DNA-topoisomerase II cross-linking activity as an indicator of topoisomerase II-DNA cleavable complex formation were evaluated. The pyrimidocarbazoles possessed high in vitro and in vivo potencies. Compound 26 (ER-37326), 8-acetyl-2-[2-(dimethylamino)ethyl]-1H-pyrimido[5,6,1-jk]carbazole-1,3(2H)-dione, showed in vitro growth inhibitory activity with respective IC(50) values of 0.049 microM and 0.35 microM against mouse leukemia P388 and human oral cancer KB. In vivo, this compound inhibited the tumor growth of mouse sarcoma M5076 implanted into mice with T/C values of 42% and 13% at 3.13 and 6.25 mg/kg/d respectively without significantly affecting the body weight. In addition, compound 26 (ER-37326) increased the formation of DNA-topoisomerase II cross-linking in P388 cells.     

One-way isomerization and internal rotation in anthrylethylenes in the excited triplet state

1-(2-Anthryl)-2-(bromophenyl)ethylene and 1-(2-anthryl)-2-(4-methoxyphenyl)ethylene undergo cis→trans one-way isomerization in the excited triplet state through an adiabatic process from the cis-triplet to the trans-triplet states. The trans-isomers of these compounds undergo one-way internal rotation in the excited triplet state with an activation barrier of }7 kcal mol^?1 and a frequency factor of }10¹² s^?1, while no internal rotation takes place in the excited singlet state.     

Efficient and beta-Stereoselective Synthesis of 4(5)-(beta-D-Ribofuranosyl)- and 4(5)-(2-Deoxyribofuranosyl)imidazoles(1)

A synthetic route to 4(5)-(beta-D-ribofuranosyl)imidazole (1), starting from 2,3,5-tri-O-benzyl-D-ribose (5), was developed via a Mitsunobu cyclization. Reaction of 5 with the lithium salt of bis-protected imidazole afforded the corresponding 5-ribosylimidazole 7RS. Hydrolysis of 7RS gave a 1:1 mixture of diol isomers 8R and 8S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8RS using N,N,N',N'-tetramethylazodicarboxamide and Bu(3)P exclusively afforded benzylated beta-ribofuranosyl imidazole 9beta in 92% yield, accompanied by alpha-anomer 9alpha, in a ratio of 26.3:1. The configuration of 9beta was established by X-ray crystallography of ethoxycarbonyl derivative 10beta. Reductive debenzylation of 9beta over Pd/C was carried out, and the synthesis of 1 was attained from starting 5 in four steps and 87% overall yield. This synthetic methodology was extended to the synthesis of 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole (2). Mitsunobu cyclization of a 1:1 mixture of the corresponding diol isomers 14RS produced 15beta and 15alpha in a ratio of 5.4:1. The synthesis of 2 was attained in a 59% overall yield from the starting 3,5-di-O-benzyl-2-deoxy-D-ribose (12). beta-Stereoselective glycosylation in the key step is discussed and explained by intramolecular hydrogen bonding between an NH in the imidazole and the oxygen functional group in the sugar moiety.     

Ductility improvement of Zr-Cu-Ni-Al glassy alloy

We studied the relationship between the phase diagrams and formation of crystalline inclusions in cast samples in order to improve the ductility of Zr-Cu-Ni-Al bulk amorphous alloy. A Zr₅₀Cu₄₀Al₁₀ bulk amorphous alloy with a composition close to the ternary eutectic point has no crystalline inclusions and possesses superior mechanical properties of tensile strength σ_B=2000 MPa, Young’s modulus E=107 GPa and Vickers hardness HV=580. Oxygen embrittlement of Zr-Cu-Ni-Al bulk amorphous alloys can be avoided in the Zr₅₀Cu₃₀Ni₁₀Al₁₀ bulk amorphous alloy, which exhibits superior ductility and resistance to oxidation. Furthermore, we tried to improve ductility by cold rolling by making use of the apparent work-softening phenomenon of Zr-Cu-Ni-Al bulk amorphous alloys. Preliminary studies indicated that cold rolling to produce a fine slip-band structure, which enabled uniform deformation and superior deformability, is an important procedure for improving the ductility of Zr-Cu-Ni-Al bulk amorphous alloys.     

Rhodium-Catalyzed Intermolecular [4+2] Cycloaddition of Unactivated Substrates

No electron-withdrawing or electron-releasing substituents are necessary for the substrates in the rhodium-catalyzed [4+2] cycloaddition reaction between a vinylallene and an ordinary alkyne under mild conditions [Eq. (1)]. The use of the strongly electron-accepting P[OCH(CF₃)₂]₃ ligand affords the optimal rhodium catalyst. cod = 1,5-cyclooctadiene.     

Study on the Morphological Change of Growing Ag Crystallites by in-situ SEM Observation

The morphology of the initial growth stage of Ag thin films on Mo(110) substrate was investigated in-situ by the scanning electron microscope (SEM). A great majority of the Ag crystallites showed a truncated Wulff's equilibrium shape of the face-centered-cubic (fcc) structure with epitaxial orientation [1 0]Ag//[11 ]Mo, (111)Ag//(110)Mo with the substrate temperature of 400 °C. In-situ SEM observation during the growth revealed two kinds of particular morphological change of Ag crystallites, namely (1) rotation of an Ag crystallite and (2) reformation of the crystal faces of the Ag crystallite. However, a small number of Ag crystal particles showed Wulff-polyhedron truncated by the (100) plane parallel to the substrate surface (oriented to the 〈100〉 axis normal to the substrate surface).     

Characteristic parameters and classification of one-dimensional cellular automata

We present definitions of characteristic parameters and discuss a classification of one-dimensional cellular automata. The parameters: probability of active sites, capacity dimension and spreading rate of difference patterns are defined on the image of the configuration space of all site states under a rule function of time evolution. On study of 2-state, 3-neighbor cellular automata we propose a new classification scheme of the rules, which gives quantitative grounds for the Wolfram's phenomenological classification.