Optical 2-benzyl-5-hydroxy-4-oxopentanoic acids against carboxypeptidase A:Synthesis,kinetic evaluation and X-ray crystallographic study

2-Benzyl-5-hydroxy-4-oxopentanoic acid 1 and its enantiomers were designed,synthesized and assayed for inhibitory activity against carboxypeptidase A(CPA,EC 3.4.17.1).To verify the role of the terminal hydroxyl group in 1 binding to CPA,2-benzyl-5- benzyloxy-4-oxopentanoic acid 2 was also synthesized and evaluated.The inhibition constants show that both L-1 and D-1 were shown to have strong binding affinity with L-1 being more potent than its enantiomer by 165-fold.On the other hand,the inhibition constant ...

Reaction of 1,1-Di-p-methoxyphenyl-2,2-dinitroethylene and 1,1-Di-O-methoxyphenyl-2,2-dinitroethylene with 1-Benzyl-1,4-dihydroni-cotinamide:Evidence for Concerted Electron-hydrogen Atom Trans-fer Mechanism

Di-p-methoxyphenyl-2, 2-dinitroethylene reacts with 1-benzyl-1, 4-dihydronico- tinamide (BNAH) in deaerated acetonitrile to give 1, 1-di-p-methoxyphenyl-2, 2-dinitroethane, while 1, 1-di-O-methoxyphenyl-2, 2-dinitroethylene fails to react with BNAH under the same conditions, which provides evidence for a concerted electron-hydrogen atom transfer mechanism.

Synthesis, Characterization and X-ray Crystal Structure of 2-Benzyl-7-butoxyl-9-isobutyl-1-methyl-β-carboline Bromide

2-Benzyl-7-butoxyl-9-isobutyl-1-methyl-β-carboline bromide（H-2-65） was synthesized by the reaction of Harmine with 1-iodobutane via N9-alkylation, demethyl and N2-quaternarization to obtain the new compound. The results demonstrate that H-2-65 has more remarkable anticancer activities in vitro. The results of 1H NMR, 13 C NMR, DEPT, g COSY, g HSQC, g HMBC, MS, single-crystal X-ray diffraction and elemental analysis showed that the title compound crystallizes in the triclinic system, space group P1 with a = 9.545（5）, b = 11.724（5）, c = 11.839（6） , α = 77.530（6）, β = 87.169（6）, γ = 72.823（5）o, Z = 2, V = 1235.8（10）3, Dc = 1.294 g·cm-3, F（000） = 504, the final R = 0.0453, wR = 0.1262 and S = 1.044.

Weak Interactions and 2D Layer Structure of a New Ion-pair Complex Bis(1-benzyl-4-methylquinolinium)-bis(maleonitriledithiolato)nickel(Ⅱ)

A new ion-pair complex, [BzMeQ1]2[Ni（nmt）2]1（[BzMeQ1]^＋ = 1-benzyl-4-ntethylquino- linium, mnta- -- maleonitriledithiolate） has been synthesized and structurally characterized by IR, ESI-MS and X-ray diffraction methods. Complex 1 is of triclinic, space group PI, with a = 9.079（2）, b = 10.154（2）, c = 11.243（2）A, α= 81.58（1）, β= 69.63（1）, γ = 68.02（1）°, V= 940.1（3）A3, Dc = 1.427 g/cm^3, Z = 1, F（000） = 418 and R = 0.0442. A 2D layer structure is formed via the cation-cation π…π and C-H…π interactions observed in the solid state of the complex.

Metal-free directed C-H borylation of 2-(N-methylanilino)-5-fluoropyridines and 2-benzyl-5-fluoropyridines

A novel method for metal-free C-H borylation of 2-(N-methylanilino)-5-fluoropyridines and 2-benzyl-5-fluoropyridines has been reported. The 5-fluoropyridine directed borylation reaction exhibited high efficiency and site exclusivity. The useful protocol could be executed on a gram-scale easily and the borylated products showed good derivatization applications. Moreover, the practicality of the strategy was expanded by the fact that the directing group could be removed in an acceptable yield.

Structure-based design and synthesis of 5-benzyl-2-phenylpyrimidin-4(3H)-one derivatives as novel MEK1 inhibitors

Previous studies have shown that Ras/Raf/MEK/ERK signaling pathway is up-regulated in almost all cancer cells.Blocking of this pathway by MEK inhibition is an efficient therapeutic approach of cancer.In the present study,we described the discovery of 5-benzyl-2-phenylpyrimidin-4（3 H）-one as a novel skeleton of allosteric MEK inhibitor.All acquired target compounds exhibited modest potency to inhibit MEK1 in Raf-MEK cascading assay,and docking studies revealed that the binding mode of the most potent compound（SJ3） was very similar to that of the well known diarylamine-based inhibitor（PD0325901）.The results provided valuable guidance for further optimizations on this novel scaffold to achieve druggable molecules.

Synthesis of Chiral α-Benzyl-β^(2)-hydroxy Carboxylic Acids through Iridium-Catalyzed Asymmetric Hydrogenation of α-Oxymethylcinnamic Acids

An asymmetric hydrogenation of α-oxymethylcinnamic acids was developed by using chiral spiro phosphineoxazoline/iridium complexes as catalysts to prepare β^(2)-hydroxycarboxylic acids with high reactivity(TON up to 2000)and excellent enantioselectivity(up to 99.5%ee).By using this highly efficient asymmetric hydrogenation as a key step,a concise total synthesis of natural product homoisoflavone(S)-(+)-4 was accomplished.