Bioisostere of Sulfonyl Moiety-The Synthesis of New ALS Inhibitors N-(Asymmetry Disubstituted Phosphoryl)-N'-(4,6-dimethoxypyrimidin-2-yl) Ureas

IntroductionAcetolactatesynthase(ALS)isthefirstcommonenzymeinthebiosyntheticpathwayforthebranched-chainaminoacidsvaline,leucineandisoleucine.Itisaveryeffectivetargetsiteforherbicidalaction,whichistheselectedmodeofactionasitisspecificforplantsanddoesnotaffectmammals.Sulfonylureaherbicidesareanewclassofherbicidesdiscoveredinthemid-l97O'sl.ItsmodeofactionhasbeenestablishedtobeinhibitorytowardALS2.Muchattentionhasbeenfocusedonthiskindofcompounds,sincetheyhaveexcellentactivity,ahighdegreeofseIe…     

Synthesis, stereochemistry confirmation and biological activity evaluation of a constituent from Isodon excisus

A synthesis and stereochemistry confirmation of a constituent recently isolated from the whole plant Isodon excisus is reported. An enantioselective catalytic boron-mediated reduction of an α-bromoketone was utilized in the key synthetic transformation. The methodology described herein was also used for the synthesis of the natural product's enantiomer and several derivatives. In addition, the compounds were evaluated for inhibitory activity in a caspase induction assay. The natural product was found to be devoid of activity, but several derivatives had moderate inhibitory activity (EC₅₀<1 μM).     

Novel dual inhibitors against FP-2 and PfDHFR as potential antimalarial agents: Design,synthesis and biological evaluation

A series of novel 2,4-diaminopyrimidine-modified compounds was designed and synthesized. Compound 14 showed micromolar dual inhibitory effect on both FP-2 and PfDHFR, and potential inhibition to the proliferation of P. falciparum 3D7 strain and chloroquine-resistant P. falciparum Dd2 strain.     

Synthesis of furan 4′-thio-C-nucleosides, their methylsulfonium and sulfoxide derivatives. Evaluation as glycosidase inhibitors

A series of furan C-nucleosides having a sulfur atom in the sugar ring were synthesised. The α and β anomers of 3-ethoxycarbonyl-2-methyl-5-(4′-thio-d-erythrofuranosyl)furans 10 and 11 were obtained by acid treatment of (4′-S-acetyl-4′-thio-d-arabino-tetritol-1-yl)furan 9. Oxidation of 10 with m-chloroperbenzoic acid gave sulfoxide 12 as one epimer at the sulfur atom whereas 11 was transformed into sulfoxide 13 as an epimeric mixture. S-Methylation of 10 and 11 with methyl triflate led to sulfonium salts 14 and 15. The prepared compounds were found to be moderate inhibitors of α-l-fucosidase.     

合成天然产物曲古抑菌素A的新方法

报道了一条组蛋白去乙酰化酶抑制剂曲古抑菌素A的有效合成路线. 通过L-脯氨酸催化对硝基苯甲醛与丙醛的羟醛缩合反应, 高立体选择性地构建了目标分子的手性中心, 羟醛缩合产物的ee值大于99%, anti∶syn＝16∶1. 随后的合成过程中无消旋化现象, 合成的曲古抑菌素A是单一R型异构体, ee值大于99%.     

Synthesis of 8-vinyladenosine 5′-di- and 5′-triphosphate: evaluation of the diphosphate compound on ribonucleotide reductase

The synthesis of 5′-di- and 5′-triphosphate of 8-vinyladenosine to be tested on ribonucleotide reductases requires the modification of known methods. The phosphate group was introduced by treatment with an in situ generated chlorophosphite. Protection of the 2′,3′ diol with acetyl groups suppressed depurination during acid removal of the phosphotriester protecting groups. The di- and triphosphate compounds were obtained by treatment of the activated adenylic acid with phosphate or pyrophosphate anions followed by removal of the acetate protecting groups. Preliminary studies were conducted on Escherichia coli ribonucleotide reductase and have shown that the diphosphate compound is efficiently reduced.     

MMI作为铜的盐酸酸洗缓蚀剂作用机理的研究

用失重法研究了N-甲基-2-巯基咪唑（MMI）在5％盐酸中对铜的酸洗缓蚀性能.探讨了温度和MMI浓度对缓蚀效果的影响，从中得出了MMI在铜表面的吸附等温式，计算了吸附热及MMI的加入对铜在盐酸中腐蚀反应活化能的影响，进而探讨了MMI对铜缓蚀作用的机理.结果表明， 30 ℃下，在5％盐酸中，当MMI的浓度在3 mmol•L－1和8 mmol•L－1之间时,缓蚀率随MMI浓度的增加而迅速增加，当浓度达到8 mmol•L－1时，缓蚀率趋于定值，而当浓度小于3 mmol•L－1时， MMI的加入会加速铜的腐蚀；吸附在铜表面的MMI分子间的作用力整体表现为引力； MMI在铜表面的吸附是吸热反应； MMI的加入降低了铜的腐蚀反应活化能.     

Synthesis and biological activity of fluorinated 2-amino-4-aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazoles

The heterocyclic nucleus s-triazino[1,2-a]benzimidazole has been reported to exhibit antibacterial activity. In this study, seven new 3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole derivatives were prepared via cyclocondensation between 2-guanidinobenzimidazole and fluorine substituted (including trifluoromethyl) benzaldehydes. The structures of all the compounds were confirmed by ¹H, ¹³C NMR and IR spectral data. Spectral data also suggested the existence of various tautomeric forms of the fluorine-containing s-triazino[1,2-a]benzimidazole compounds. The synthesized compounds were also screened for antibacterial and bovine dihydrofolate reductase (DHFR) inhibitory activities. The compound 3g substituted with a 3′,5′-bis(trifluoromethyl)phenyl moiety demonstrated the best antibacterial activity in the series. None of the tested compounds significantly inhibited bovine DHFR.     

The Biological Effects of Forsythia Leaves Containing the Cyclic AMP Phosphodiesterase 4 Inhibitor Phillyrin

Forsythia fruit (Forsythia suspensa Vahl (Oleaceae)) is a common component of Kampo medicines for treating the common cold, influenza, and allergies. The main polyphenolic compounds in the leaves of F. suspensa are pinoresinol β-d-glucoside, phillyrin and forsythiaside, and their levels are higher in the leaves of the plant than in the fruit. It is known that polyphenolic compounds stimulate lipid catabolism in the liver and suppress dyslipidemia, thereby attenuating diet-induced obesity and polyphenolic anti-oxidants might attenuate obesity in animals consuming high-fat diets. Recently, phillyrin was reported as a novel cyclic AMP phosphodiesterase 4 (PDE4) inhibitor derived from forsythia fruit. It was expected that the leaves of F. suspensa might display anti-obesity effects and serve as a health food material. In this review, we summarized our studies on the biological effects of forsythia leaves containing phillyrin and other polyphenolic compounds, particularly against obesity, atopic dermatitis, and influenza A virus infection, and its potential as a phytoestrogen.     

Synthesis of phosphonocinnamic thioesters, substrate analogues of cinnamoyl-CoA reductase, a key enzyme in the lignification process

The one-pot transesterification of diethylarylvinylphosphonates with N-acetylcysteamine has been achieved using phosphonochloridates as intermediates. Reaction of phosphonodiesters with (COCl)₂ gave the corresponding chlorinated compounds, which were coupled with N-acetylcysteamine in presence of Et₃N.