Synthesis of polycyclic pyridazinediones as chemiluminescent compounds

Reactions of 1,3-disubstituted 5-aminopyrazole-4-carbonitrile derivatives 3a-o with dimethyl acetylenedicarboxylate in the presence of potassium carbonate in dimethyl sulfoxide gave the corresponding dimethyl 1,3-disubstituted pyrazolo[3,4-b]pyridine-5,6-dicarboxylates 4a-o which were allowed to react with excess hydrazine hydrate under ethanol refluxing conditions followed by heating at 250-300° to give 1,3-disubstituted 4-amino-1H-pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-diones 7a-s in good yields. Similarly, 1,3-disubstituted 4-hydroxy-1H-pyrazolo[4′3′:5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-diones 10a-c were obtained from alkyl 1,3-disubstituted 5-aminopyrazole-4-carboxylates 8a-c . These tricyclic pyridazine derivatives were alternatively synthesized from 4-hydroxypyrrolo[3,4-e]pyrazolo[3,4-b]pyridine-5,7-diones 13a-c prepared by reactions of 5-aminopyrazoles (8e-g) with methyl 1-methyl-4-methylthio-2,5-dioxo-1H-pyrrole-3-carboxylate (11a) followed by the Gould/Jacobs reaction. 1-Methyl-4-methylthio-2,5-dioxo-1H-pyrrole-3-carbonitrile smoothly reacted with 2-aminobenzimidazoles to give the corresponding 5-amino-3-methyl-1H-pyrrolo[3′4′:4,5]pyrimido[1,2-a]benzimidazole-1,3(2H)-diones 16a-e , which were readily converted to the desired 12-aminopyridazino[4′,5′:4,5]pyrimido-[1,2-a]benzimidazole-1,4(2H,3H)-diones 17a-e in good yields. Other pyridazinopyrimidine derivatives were also obtained by the reaction of the corresponding 2-aminoheterocycles with the maleimide in good yields. Substituted anilines reacted 11b in refluxing methanol to give the corresponding methyl 4-phenylamino-1-methyl-2,5-dioxo-1H-pyrrole-3-carboxylates 25a-e which were converted in good yields to 2-methylpyrrolo[3,4-b]quinoline derivatives 26a-e by heating in diphenyl ether. Reaction of 26a-c with hydrazine hydrate gave 10-hydroxypyridazino[4,5-b]quinoline-1,4(2H,3H)-diones 27a-e in good yields. The desired 10-aminopyridazino[4,5-b]pyridazine-1,4(2H,3H)-diones 30a-e were obtained in good yields by the chlorination of 4a-e with phosphorus oxychloride followed by aminolysis with 28% ammonium hydroxide. Some pyridazino[4,5-a][2.2.3]cyclazine-1,4(2H,3H)-diones 37a,b as luminescent compounds were synthesized via several steps from indolizine derivatives. The key intermediates, dimethyl 6-dimethylamino[2.2.3]cyclazine-1,2-dicarboxylates 34, 36 , were synthesized by the [8 + 2] cycloaddition reaction of the corresponding 7-dimethylaminoindolizines 33, 35 with dimethyl acetylenedicarboxylate in the presence of Pd-C in refluxing toluene. Some were found to be more efficient than luminol in light production. 4-Amino-3-methylsufonyl-1-phenyl-1H-pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-dione (7r) , 10-hydroxypyridazino[4,5-b]-quinoline-1,4(2H,3H)-diones 27a-e , and 10-aminopyridazino[4,5-b]quinoline-1,4(2H,3H)-diones 30a-e showed the greatest chemiluminescence intensity in the presence of hydrogen peroxide peroxidase in a solution of phosphate buffer at pH 8.0.     

Temperature and Oxygen Partial Pressure Dependences of the Surface Tension of Liquid Sn–Ag and Sn–Cu Lead-free Solder Alloys

Summary. Temperature dependence of the surface tension of liquid Sn–Ag and Sn–Cu base lead-free solder alloys and oxygen partial pressure dependence of liquid Sn–Ag alloy were evaluated using the experimental data obtained, respectively, by the constrained drop method and the sessile drop method in the previous studies [1, 2]. The temperature dependences of the surface tension have maximum positive values when the mol fraction of Ag and Cu is about 0.7, while those for pure liquid Sn, Ag, and Cu have negative values. The calculated values based on Butler’s equations were found to be in reasonable agreement with those of the experimental data. The oxygen partial pressure dependences of the surface tension of liquid Sn–Ag alloys at 1253 K have a minimum value when the mol fraction of Ag is about 0.9 and the oxygen partial pressure is less than about 10⁻¹³ atm. From this, it is considered that the oxygen adsorption increased by adding Ag to Sn when the mol fraction of Ag is less than 0.9.     

The crystal structure of the monohydrate R2Mo6O21·H2O (R=Pr, Nd, Sm, and Eu): a layer structure containing disordered [Mo2O7] groups

Although R₂O₃:MoO₃=1:6 (R=rare earth) compounds are known in the R₂O₃-MoO₃ phase diagrams since a long time, no structural characterization has been achieved because a conventional solid-state reaction yields powder samples. We obtained single crystals of R₂Mo₆O₂₁·H₂O (R=Pr, Nd, Sm, and Eu) by thermal decomposition of [R₂(H₂O)₁₂Mo₈O₂₇]·nH₂O at around 685-715 °C for 2 h, and determined their crystal structures. The simulated XRD patterns of R₂Mo₆O₂₁·H₂O were consistent with those of previously reported R₂O₃:MoO₃=1:6 compounds. All R₂Mo₆O₂₁·H₂O compounds crystallize isostructurally in tetragonal, P4/ncc (No. 130), a=8.9962(5), 8.9689(6), 8.9207(4), and 8.875(2) Å; c=26.521(2), 26.519(2), 26.304(2), and 26.15(1) Å; Z=4; R₁=0.026, 0.024, 0.024, and 0.021, for R=Pr, Nd, Sm, and Eu, respectively. The crystal structure of R₂Mo₆O₂₁·H₂O consists of two [Mo₂O₇]²⁻-containing layers (A and B layers) and two interstitial R(1)³⁺ and R(2)³⁺ cations. Each [Mo₂O₇]²⁻ group is composed of two corner-sharing [MoO₄] tetrahedra. The [Mo₂O₇]²⁻ in the B layer exhibits a disorder to form a pseudo-[Mo₄O₉] group, in which four Mo and four O sites are half occupied. R(1)³⁺ achieves 8-fold coordination by O²⁻ to form a [R(1)O₈] square antiprism, while R(2)³⁺ achieves 9-fold coordination by O²⁻ and H₂O to form a [R(2)(H₂O)O₈] monocapped square antiprism. The disorder of the [Mo₂O₇]²⁻ group in the B layer induces a large displacement of the O atoms in another [Mo₂O₇]²⁻ group (in the A layer) and in the [R(1)O₈] and [R(2)(H₂O)O₈] polyhedra. A remarkable broadening of the photoluminescence spectrum of Eu₂Mo₆O₂₁·H₂O supported the large displacement of O ligands coordinating Eu(1) and Eu(2).     

Four new cycloartane glycosides from Aquilegia vulgaris and their immunosuppressive activities in mouse allogeneic mixed lymphocyte reaction

Four new cycloartane glycosides, named aquilegiosides C-F, were isolated from the dried aerial parts of Aquilegia vulgaris. Their structures were determined by two dimensional (2D) NMR spectroscopic analysis and chemical evidence. Aquilegiosides C-F suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction with IC(50), ranging from 3.7x10(-5) to 2.2x10(-4) M.     

Antiproliferative constituents from Umbelliferae plants VI. New ursane-type saikosaponin analogs from the fruits of Bupleurum rotundifolium

The MeOH extract of the fruits of Bupleurum rotundifolium showed inhibitory activity against human gastric adenocarcinoma (MK-1) cell growth (GI(50): 6.25 microg/ml). From this extract, 10 new ursane-type triterpene glycosides viz. three 3-O-triosides (called rotundifoliosides A, I, and J) of 13beta,28-epoxy-3beta,16alpha-dihydroxyurs-11-ene, two (G and H) of 13beta,28-epoxy-3beta,16alpha,23-trihydroxyurs-11-ene, two (E and F) of 13beta,28-epoxy-3beta,16alpha,21beta-trihydroxyurs-11-ene, two (B and C) of 3beta,11alpha,16alpha,28-tetrahydroxyurs-12-ene, and one (D) of 3beta,11alpha,28-trihydroxy-15alpha,16alpha-epoxyurs-12-ene were isolated in addition to 16 new oleanane-type triterpene glycosides (rotundiosides J-Y), echinocystic acid 3-O-sulfate and 3 known oleanane-type triterpene glycosides (rotundiosides A, F and G). The isolation, structures and antiproliferative activity of the new ursane-type triterpene glycosides against MK-1, human uterus carcinoma (HeLa), and murine melanoma (B16F10) cell lines are described with some comments on the structural requirements for their activity.     

Total synthesis of the antitumor acetogenin mosin B: desymmetrization approach to the stereodivergent synthesis of threo/trans/erythro-type acetogenins

A total synthesis of the threo/trans/erythro-type acetogenin mosin B and one of its diastereomers has been achieved. The carbon skeleton is assembled in a convergent fashion from two segments (a THF ring segment and a gamma-lactone segment) through the Nozaki-Hiyama-Kishi reaction. The THF ring segment was stereoselectively constructed by a stereodivergent synthesis starting from a common intermediate (4-cyclohexene-1,2-diol) based on a desymmetrization strategy. The gamma-lactone segment was synthesized by coupling a triflate and a chiral alpha-sulfenyl gamma-lactone. By virtue of these synthetic results, we suggest that the absolute configuration of natural mosin B is 1 a. Antiproliferative effects of 1 a and 1 b were also investigated.     

Mössbauer study of paramagnetic relaxation effect in mixed crystals: High spin Fe3+ compounds diluted in diamagnetic hosts

The⁵⁷Fe Mössbauer spectra were measured in mixed crystals with different types of chemical bonding and crystal structure, i.e., (Fe,Al)(acac)₃, (Fe,Co)(acac)₃, K₃[(Fe,Al)(ox)₃]3H₂O, and NH₄(Fe,Al)(SO₄)₂12H₂O. The broadening of Mössbauer linewidth with increasing Fe³⁺–Fe³⁺ distance became less enhanced in the order: (Fe,Al)(acac)₃>(Fe,Co)(acac)₃, or K₃[(Fe,Al)(ox)₃]3H₂O>(Fe,Al)(acac)₃>NH₄(Fe,Al)(SO₄)₂12H₂O. Furthermore, it was found that the broadening of the linewidth was larger in neat tris (-diketonato) iron(III) complexes than in (Fe,Al)(acac)₃. Based on these results, the determining factors of the paramagnetic relaxation time other than Fe³⁺–Fe³⁺ distance and temperature were examined in terms of the Mössbauer linewidth as an indicator.     

Novel Reaction Route Including Enzymic Reaction For A Synthesis Of A Branched Polysaccharide

Abstract

Stereoselective synthesis of α-D-glucosyl-branching polysaccharide by chemical and enzymic reactions was investigated. Ring-opening polymerization of 1,6-anhydro-3-O-benzoyl-2,4-di-O-benzyl-β-D-glucopyranose (1) with PF₅ as catalyst at low temperature gave a highly stereoregular polymer, which was converted to 2,4-diO-benzyl-(1→6)-α-D-glucopyranan by debenzoylation with sodium methoxide. The polymer was glucosylated according to the glycosyl imidate method. Deprotection of the branched polysaccharide was carried out with sodium in liquid ammonia at -78 °C to give a (1→6)-α-D-glucopyranan having α-D-glucopyranosyl and β-D-glucopyranosyl branches. Only the β-D-glucopyranosyl branch of the polymer was completely removed by enzymatic hydrolysis by the use of cellulase to provide stereoregular (1→6)-α-D-glucopyranan having an α-D-glucopyranosyl branch at the C-3 position. Polymers were characterized by optical rotation, NMR spectroscopy, GPC, and X-ray diffractometry.     

Self‐Assembly and Host–Guest Chemistry of a 3.5‐nm Coordination Nanotube

Upon complexation with Pd^II ions, precisely designed strandlike ligands with two tris(3,5‐pyridine) units at both terminals were assembled, with the aid of a linear template molecule, into a discrete tubular complex with a length of 3.5 nm. The high stability and the well‐defined structure of the coordination nanotube were revealed by NMR spectroscopy, cold‐spray ionization MS, and single‐crystal X‐ray analysis. Guest lengths were discriminated by the tube: When the association of strandlike guest molecules, in which two biphenylene units are linked with an (OCH₂CH₂)_n linker, were compared, the tube selectively recognized an appropriate guest whose length was comparable to that of the tube. Tetrathiafulvalene (TTF)‐terminated linear guests were directly oxidized to TTF²⁺ in the tube, but reduced stepwise via TTF^+? outside the tube.