Ultrasound-promoted one-pot four-component synthesis of novel biologically active 3-aryl-2,4-dithioxo-1,3,5-triazepane-6,7-dione and their toxicity investigation

We have described a novel four-component reaction (4MCR) between oxalyl chloride 1, anilines 2a–h, and two molecules of ammonium thiocyanate 3 in acetone under ultrasound irradiation to give 3-aryl-2,4-dithioxo-1,3,5-triazepane-6,7-diones. A synthetically useful ultrasound effect was observed and title products were obtained in high yields after 15–35?min sonication. Our procedure compared to the conventional heating method has the benefit of higher reaction yields and shorter reaction times. The IR spectra showed the presence of N–H, C═O and C═S groups in these compounds and ¹H, ¹³C NMR and Mass spectral results verified their structures. Cellular investigations showed that these compounds are toxic toward cancer cells.     

Carbon resistance of xNi/HTASAO5 catalyst for the production of H2 via CO2 reforming of methane

xNi/HTASAO5 catalysts (x = 2.5, 3.3, 4.4, 5.8, 8.2) were prepared for CO₂ reforming of methane. No crystalline nickel species formed on the catalysts with lower nickel content (≤4.4%), and large Ni⁰ crystallite formed on 5.8% (10 nm) and 8.2 wt%Ni/HTASAO5 (17 nm), whereas the surface concentration of Ce³⁺ decreased with Ni loading. The initial conversion of CH₄ increased from 29.5% to 46.9% with Ni loading. The xNi/HTASAO5 (x ≤ 4.4%) performed stably in the reaction due to the presence of dispersed Ni species and high surface Ce³⁺ content without coke formation, however, 5.8% and 8.2 wt%Ni/HTASAO5 exhibited decreased activity with time on stream, because of the formation of large Ni particles with lower surface Ce³⁺, leading to carbon accumulation. Thus, CH₄ conversion stabilized at about 43% and no carbon formed on 4.4 wt%Ni/HTASAO5 with optimum Ni loading.     

Synthesis and Biological Activity of New Brassinosteroid Analogs of Type 24-Nor-5β-Cholane and 23-Benzoate Function in the Side Chain

Brassinosteroids are polyhydroxysteroids that are involved in different plants’ biological functions, such as growth, development and resistance to biotic and external stresses. Because of its low abundance in plants, much effort has been dedicated to the synthesis and characterization of brassinosteroids analogs. Herein, we report the synthesis of brassinosteroid 24-nor-5β-cholane type analogs with 23-benzoate function and 22,23-benzoate groups. The synthesis was accomplished with high reaction yields in a four-step synthesis route and using hyodeoxycholic acid as starting material. All synthesized analogs were tested using the rice lamina inclination test to assess their growth-promoting activity and compare it with those obtained for brassinolide, which was used as a positive control. The results indicate that the diasteroisomeric mixture of monobenzoylated derivatives exhibit the highest activity at the lowest tested concentrations (1 × 10⁻⁸ and 1 × 10⁻⁷ M), being even more active than brassinolide. Therefore, a simple synthetic procedure with high reaction yields that use a very accessible starting material provides brassinosteroid synthetic analogs with promising effects on plant growth. This exploratory study suggests that brassinosteroid analogs with similar chemical structures could be a good alternative to natural brassinosteroids.     

Development of Selective TGR5 Ligands Based on the 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalene Skeleton

TGR5, a G-protein-coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N-(2-chlorophenyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC₅₀ value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia.     

Pd2(dba)3-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4] thiadiazole with substituted anilines at conventional heating in Schlenk tube

ABSTRACT

An efficient Pd₂(dba)₃-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4]thiadiazole using conventional heating is reported. The C5-bromoimidazo[2,1-b][1,3,4]thiadiazole was synthesized using a multistep approach which started by cyclization of thiosemicarbazide with a carboxylic acid to give 2-amino[1,3,4]thiadiazoles which were further treated with 2-haloketones to give imidazo[2,1-b][1,3,4]thiadiazoles. Then, the bromination of imidazothiadiazole was done using N-bromosuccinimide to give the C5-bromo-imidazo[2,1-b][1,3,4]thiadiazole. Afterward, various C-N bond-forming approaches were attempted such as S_NAr, Cu(I), Cu(II), Pd(OAc)_2, Pd₂(dba)₃ catalyst with different ligand, additive, base, solvent and temperature conditions. Out of various approaches used, only Buchwald Hartwig amination, performed with conventional heating, gave N-arylamine-5-imidazothiadiazoles. Then, 10 different anilines with different electron-withdrawing and donating groups at different positions were employed to examine the scope and limitations of the method. Salient features of this method include conventional heating in a Schlenk tube as the reaction condition, the absence of the use of toxic isocyanides, the wide nature of substituent tolerance with anilines, and moderately good product yields.     

双时效对Ti-4Al-5Mo-6Cr-5V-1Nb合金显微组织和力学性能的影响

研究了固溶、固溶后单时效以及固溶后双时效处理对Ti-4Al-5Mo-6Cr-5V-1Nb合金组织和力学性能的影响。结果表明,820℃下固溶0.5 h后,合金中的α相完全溶解;单/双时效合金的硬度均随时效时间增加先升高后降低;合金经300℃/8 h+500℃/8 h双时效处理后可达到4580 MPa的峰值硬度(HV),1462 MPa抗拉强度以及3.4%延伸率,其强度比原始合金高6%,也高于单时效合金。界面能计算结果表明ω相使α相形核的阻力降低50%,促进了α相的析出并细化α板条,从而提升合金的硬度,强度及塑性。     

含La2O3奥氏体不锈钢堆焊合金层晶粒细化机制及对其耐腐蚀、磨损性能的影响

目的 通过在超低碳Cr19Ni10不锈钢堆焊合金中加入稀土氧化物La2O3，细化其微观组织，获得力学性能、耐腐蚀性能和耐磨性能等综合性能优良的堆焊合金层。方法 采用添加La2O3的超低碳Cr19Ni10不锈钢焊条制备了四种不锈钢堆焊合金。采用X射线荧光光谱、红外碳硫分析仪和X射线衍射分析仪，对堆焊合金层的元素组成和相组成进行了测定。采用金相显微镜和晶粒度统计软件，对堆焊合金层的微观组织形貌进行观察，并对晶粒度进行了统计分析。采用显微维氏硬度计和纳米压痕仪对堆焊合金层的硬度和杨氏模量进行了测定。采用电化学工作站和CSM摩擦磨损试验机对堆焊合金层的耐腐蚀性能和耐磨性能进行了评价，并且采用白光共聚焦显微镜对磨损后的磨痕形貌和尺寸进行了观察和测定。采用二维晶格错配度理论，对La2O3/γ-Fe界面间的晶格错配关系进行了计算。结果 在堆焊合金层中加入La2O3，随着La2O3加入量的增加，堆焊合金层奥氏体晶粒细化越明显。当La2O3的添加量由0%增加至1.5%时，奥氏体晶粒平均面积由400 μm²减少为210 μm²。堆焊合金层加入La2O3，可以明显提高其力学性能、耐腐蚀性能和耐磨损性能。当La2O3的添加量由0%增加至1.0%时，堆焊合金层的微观硬度由180HV增加到225HV，宏观硬度由125HBS增加到150HBS，杨氏模量由186 GPa左右增加到217 GPa，腐蚀电位由?0.4 V增加到?0.25 V，磨痕深度由50 μm减小到10 μm。La2O3(001)面和γ-Fe(110)面的二维晶格错配度为8.7%(<12%)，说明La2O3可以作为γ-Fe的中等有效异质形核基底，从而细化了堆焊合金层中的奥氏体晶粒。结论 La2O3可以有效地细化奥氏体晶粒，改善堆焊合金层的力学性能，提高其耐腐蚀和耐磨损性能。但是，La2O3加入量存在一个最佳值，当La2O3的加入量为1.0%时，堆焊合金层的综合性能最好。     

Effect of α phase morphology on fatigue crack growth behavior of Ti−5Al−5Mo−5V−1Cr−1Fe alloy

Taking a Ti−5Al−5Mo−5V−1Cr−1Fe alloy as exemplary case, the fatigue crack growth sensitivity and fracture features with various tailored α phase morphologies were thoroughly investigated using fatigue crack growth rate (FCGR) test, optical microscopy (OM) and scanning electron microscopy (SEM). The tailored microstructures by heat treatments include the fine and coarse secondary α phase, as well as the widmanstatten and basket weave features. The sample with coarse secondary α phase exhibits better comprehensive properties of good crack propagation resistance (with long Paris regime ranging from 15 to 60 MPa·m^1/2), high yield strength (1113 MPa) and ultimate strength (1150 MPa), and good elongation (11.6%). The good crack propagation resistance can be attributed to crack deflection, long secondary crack, and tortuous crack path induced by coarse secondary α phase.