A series of novel thiourea derivatives were synthesized and evaluated by biological activities. Among them, compound 10e containing 3,5-bis(trifluoromethyl)phenyl moiety (R1) at the terminal thiourea and phenylamino (R2) at the terminal acyl position showed the best cytotoxic activities against seven cancer cell lines (NCI-H460, Colo-205, HCT116, MDA-MB-231, MCF-7, HepG2, PLC/PRF/5) and HUVECs. Moreover, compound 10e moderately inhibited various RTKs such as VEGFR2, VEGFR3, and PDGFRβ. Notably, 10e exhibited much better inhibitory effect of tumor formation and antiangiogenic activities than Sorafenib and Regorafenib at the same concentration. Further docking studies suggested that 10e could serve as potential candidate for cancer therapy.

目的 建立简单、绿色、高效合成结构新颖的中氮茚类化合物的方法.方法 以色酮和吡啶乙酸乙酯为底物、1,4-二氯苯为溶剂、二叔丁基过氧化物为氧化剂,在单质碘的催化下,制备中氮茚类化合物.结果 与讨论发展了一种操作简单、绿色的方法,合成了一系列结构新颖的中氮茚类化合物,产物结构经1 HNMR、13 CNMR、19 FNMR和HR-MS表征.该反应具有底物适用范围广、收率高和条件温和的优点.初步的机理研究表明反应产生了自由基中间体.

目的 建立一种通过2-芳基丙烯酸酯的脱酯氧膦化反应构建β-羰基膦酸酯的新方法.方法 在60℃、氧气条件下,以CuBr2/FeCl3作催化剂,用三乙胺作碱、二甲基亚砜为溶剂,2-芳基丙烯酸酯和亚磷酸酯发生脱酯氧膦化反应4h,以中等至较高的收率得到相应的目标产物.结果和结论 合成了一系列β-羰基膦酸酯,结构经1HNMR、”CNMR和13PNMR表征.该反应具有良好的底物普适性和官能团耐受性.

A new TEMPO-catalyzed aminophosphinoylation of ethers with amines and H-phosphine oxides was developed for the synthesis of α-aminophosphine oxides. This metal-free aminophosphinoylation reaction could be conducted under mild conditions through tandem C(sp3)-H and C(sp3)-O bond cleavage. The present method offers a facile and efficient approach to broad range of α-aminophosphine oxide derivatives in moderate to good yields with excellent functional group tolerance.

An unprecedented method for the transformation of 2-substituted acrylates into beta-ketophosphine oxides has successfully been developed via hydrochloric acid-promoted copper/iron-cocatalyzed deesterificative oxyphosphorylation under dioxygen atmosphere, simultaneously inhibiting the formation of the preceding hydroxyphosphorylation products. Through this convenient and practical process, a library of structurally diverse beta-ketophosphine oxides could be selectively and effectively obtained with broad substrate scope and good functional group tolerance under mild conditions, accompanied by chemoselective cleavage of C(sp(2))-C(C=O) bonds.

OBJECTIVE To develop a simple,effective and convenient approach for the synthesis of sulfenylindoles.METHODS Sulfenylindoles were synthesized by the combination of indoles and thiols in i-PrOH at room temperature under air in the presence of Dess-Martin periodinane.RESULTS and CONCLUSION Various sulfenylindoles were synthesized from indoles and thiols.The molecular structures of these products were characterized by 1HNMR,13CNMR and HR-MS.The present protocol has the advantages of high atom economy,mild reaction conditions and short reaction time.

OBJECTIVE To study the inhibition effects of ziyuglycoside Ⅱ on various tumor cells and the molecular mechanism underlying the ziyuglycoside Ⅱ-induced apoptosis of tumor cells.METHODS SRB method was used to measure the effect of ziyuglycoside Ⅱ on the proliferation of cancer cells in vitro and western blot was used to test influences of ziyuglycoside Ⅱ on three pathways of apoptosis.RESULTS The intracellular ROS level of MDA-MB-231 was significantly up-regulated when treated with ziyuglycoside Ⅱ,which resulted the expression of CHOP and triggered the endoplasmic reticulum stress response.Besides,we observed that the expression of Bcl-2 was downregulated while the expression of Bax was up-regulated,which suggested the activation of mitochondrial apoptosis pathway.We also noticed the up-regulation of DR4 and DR5,which associated with the activation of death receptor pathways.CONCLUSION Through the activation of three apoptosis pathways,ziyuglycoside Ⅱ can inhibit the proliferation and promote the apoptosis of tumor cells.

A copper-catalyzed direct hydroxyphosphorylation of electron-deficient alkenes with H-phosphine oxides and dioxygen is reported. The present reaction, proceeds under mild reaction conditions with good functional group tolerance, affording the facile and efficient synthesis of various beta-hydroxyphosphine oxides in a scaled-up manner with moderate to good yields. (C) 2017 Elsevier Ltd. All rights reserved.

A facile and efficient copper catalyzed one-pot method has been developed for the formation of beta-ketophosphine oxides from ketones and H-phosphine oxides under air at room temperature, in which vinylhydrazinedicarboxylate was formed as the key intermediate. Preliminary mechanistic studies indicated that the reaction might involve a radical process and carbonyl oxygen atom of beta-ketophosphine oxides came from molecular oxygen. (C) 2017 Elsevier Ltd. All rights reserved.

A new transition-metal-free PhI(OAc)2-promoted highly selective hydroboration of terminal alkynes with bis(pinacolato)diboron has been developed at room temperature under air.

OBJECTIVE To develop a simple and efficient method to construct N-benzylbenzamides.METHODS N-Benzylbenzamides could be conveniently obtained from various benzylamine derivatives via CuBr2/Ag2CO3-catalyzed oxidative amidation reaction,using TBHP as the oxidant and diethyl phosphate as the additive.RESULTS and CONCLUSION The oxidative amidation reaction of benzylamines led to a series of N-benzylbenzamides,which were characterized by 1HNMR,13 CNMR and HR-MS.The present protocol has the advantages of simple operation,readily-available starting materials and mild reaction conditions.

Macrophages are abundant in the tumor microenvironment. They are highly plastic and able to acquire pro-tumoral phenotypes in response to microenvironmental stimuli. When we treated RAW 264.7 macrophages with inhibitors of various oncogenic pathways, we found that the focal adhesion kinase (FAK) inhibitors PF573228 and TAE226 could induce cell multinucleation by suppressing furrowing and cytokinesis. This failure in cytokinesis involves Rac1, whose activity is elevated by FAK inhibitors, and the p21-activated kinases, comprising the downstream effectors of Rac. We also investigated the influence of cell multinucleation on macrophage physiology in RAW 264.7 cells. This is the first study to report that FAK inhibitors suppress furrow ingression and early cytokinesis. Of note, we found that FAK inhibitors caused a dramatic increase in pro-tumoral cytokines in multinuclear cells, suggesting the potential to convert macrophages into pro-tumoral phenotypes.

A facile copper-catalyzed one-pot method for the synthesis of β-ketophosphine oxides has been developed via aerobic oxidative coupling of ketones with P(O)–H compounds assisted by TBSOTf at room temperature.

A simple and convenient copper‐catalyzed direct oxyphosphorylation of enamides with P(O)‐H compounds and dioxygen has been developed under mild conditions. This methodology can allow the synthesis of a series of valuable β ‐ketophosphine oxides/ β ‐ketophosphonates in moderate to good yields with a broad substrate scope simply by using readily‐available starting materials.

Radix Sanguisorbae, the root of Sanguisorba officinalis L. is used as traditional Chinese medicine. In recent decades, it has been reported to be clinically effective against myelosuppression induced by chemotherapy and/ or radiotherapy. However, the underlining mechanism has not been well studied. In this work, we evaluated the hematopoietic effect of total saponins from S. officinalis L. on myelosuppressive mice induced by cyclophosphamide and by60Co-γ-irradiation and confirmed the therapeutic effect. Then, we found total saponins and their characteristic constituents Ziyuglycoside I and Ziyuglycoside II can inhibit apoptosis of TF-1 cells caused by cytokine deprivation, and promote survival of mouse bone marrow nuclear cells through focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (Erk1/2) activation in vitro. In addition, they can down-regulate macrophage inflammatory protein 2 (MIP-2), platelet factor 4 (PF4) and P-selectin secretion, which are reported to be suppressive to hematopoiesis, both in vitro and in vivo. These results suggest that promotion of survival through FAK and Erk1/2 activation and inhibition of suppressive cytokines in the bone marrow is likely to be the pharmacological mechanism underlying the hematopoietic effect of saponins from S. officinalis L.

A simple and facile copper-catalyzed synthesis of β-ketophosphine oxides via direct oxyphosphorylation of alkynes with H-phosphine oxides and dioxygen has been developed under mild conditions without any base or cocatalyst. A radical reaction pathway for the formation of β-ketophosphine oxides is proposed. An 18O labeling experiment suggested that the carbonyl oxygen atom of β-ketophosphine oxides originated from dioxygen.

A simple and highly efficient one-pot method for the construction of α-hydroxyketone phosphates from terminal alkynes and H-phosphine oxides has been developed in the presence of PhI(OAc)2 and H2O. The present protocol provides an attractive approach to α-hydroxyketone phosphates in good to high yields, with the advantages of operation simplicity, the use of commercially available materials, broad substrate scope, high atom efficiency and good tolerance to scale-up synthesis.

A simple and catalyst-free method has been developed for the construction of 6-hydroxyphosphine oxides through direct difunctionalization of alkenes with H-phosphine oxides and dioxygen under mild conditions. Preliminary mechanistic studies indicated that the hydroxyl oxygen atom of 6-hydroxyphosphine oxide originated from the dioxygen and the present reaction might involve a radical process. (C) 2016 Elsevier Ltd. All rights reserved.