5457-29-4Relevant articles and documents
Synthesis and Biological Studies of Pyrazolyl-Diamine PtII Complexes Containing Polyaromatic DNA-Binding Groups
Gama, Sofia,Mendes, Filipa,Esteves, Teresa,Marques, Fernanda,Matos, Antonio,Rino, Jose,Coimbra, Joana,Ravera, Mauro,Gabano, Elisabetta,Santos, Isabel,Paulo, Antonio
, p. 2352 - 2362 (2012)
New [PtCl(pzNN)]n+ complexes anchored by pyrazolyl-diamine (pzNN) ligands incorporating anthracenyl or acridine orange DNA-binding groups have been synthesized so as to obtain compounds that would display synergistic effects between platination and intercalation of DNA. Study of their interaction with supercoiled DNA indicated that the anthracenyl-containing complex L2Pt displays a covalent type of binding, whereas the acridine orange counterpart L3Pt shows a combination of intercalative and covalent binding modes with a strong contribution from the former. L2Pt showed a very strong cytotoxic effect on ovarian carcinoma cell lines A2780 and A2780cisR, which are, respectively, sensitive to and resistant to cisplatin. In these cell lines, L2Pt is nine to 27 times more cytotoxic than cisplatin. In the sensitive cell line, L3Pt showed a cytotoxic activity similar to that of cisplatin, but like L2Pt was able significantly to overcome cisplatin cross-resistance. Cell-uptake studies showed that L2Pt accumulates preferentially in the cytoplasm, whereas L3Pt reaches the cell nucleus more easily, as clearly visualized by time-lapse confocal imaging of live A2870 cells. Altogether, these findings seem to indicate that interaction with biological targets other than DNA might be involved in the mechanism of action of L2Pt because this compound, despite having a weaker ability to target the cell nucleus than L3Pt, as well as an inferior DNA affinity, is nevertheless more cytotoxic. Furthermore, ultrastructural studies of A2870 cells exposed to L2Pt and L3Pt revealed that these complexes induce different alterations in cell morphology, thus indicating the involvement of different modes of action in cell death.
Copper-Catalyzed Difluoromethylation of Alkyl Iodides Enabled by Aryl Radical Activation of Carbon–Iodine Bonds
Cai, Aijie,Liu, Wei,Wang, Chao,Yan, Wenhao
supporting information, p. 27070 - 27077 (2021/11/18)
The engagement of unactivated alkyl halides in copper-catalyzed cross-coupling reactions has been historically challenging, due to their low reduction potential and the slow oxidative addition of copper(I) catalysts. In this work, we report a novel strategy that leverages the halogen abstraction ability of aryl radicals, thereby engaging a diverse range of alkyl iodides in copper-catalyzed Negishi-type cross-coupling reactions at room temperature. Specifically, aryl radicals generated via copper catalysis efficiently initiate the cleavage of the carbon–iodide bonds of alkyl iodides. The alkyl radicals thus generated enter the copper catalytic cycles to couple with a difluoromethyl zinc reagent, thus furnishing the alkyl difluoromethane products. This unprecedented Negishi-type difluoromethylation approach has been applied to the late-stage modification of densely functionalized pharmaceutical agents and natural products.
Benzil compound as well as preparation method and application thereof
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Paragraph 0058; 0063, (2021/06/09)
The invention provides a benzil compound as well as a preparation method and application thereof, the structure of the benzil compound is shown as a formula I, wherein R1 is -(CH2) n-N (CX1Y1Z1) (CX2Y2Z2), n is an integer from 1 to 6, and X1, X2, Y1, Y2, Z1 and Z2 are independently selected from hydrogen or deuterium. The benzil compound provided by the invention is applied to detection of guanidine compounds, can remarkably improve the sensitivity, accuracy and stability of detection, can be used for identifying potential guanidine compounds in a to-be-detected sample, and is low in cost.
Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enecarbamates
Qian, Deyun,Bera, Srikrishna,Hu, Xile
supporting information, p. 1959 - 1967 (2021/02/06)
Chiral alkyl amines are omnipresent as bioactive molecules and synthetic intermediates. The catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enecarbamates (N-Cbz-protected enamines) and alkyl halides with high regio- and enantioselectivity. The method works for both nonactivated and activated alkyl halides and is able to produce enantiomerically enriched amines with two minimally differentiated α-alkyl substituents. The mild conditions lead to high functional group tolerance, which is demonstrated in the postproduct functionalization of many natural products and drug molecules, as well as the synthesis of chiral building blocks and key intermediates to bioactive compounds.
Multiplexed Analysis of Endogenous Guanidino Compounds via Isotope-Coded Doubly Charged Labeling: Application to Lung Cancer Tissues as a Case
Liu, Li,Chen, Yan-Zhen,Zhang, Shu-Sheng,Chen, Xiu-Ping,Lin, Guo-Qiang,Yin, Hang,Feng, Chen-Guo,Zhang, Fang
, p. 16862 - 16872 (2021/12/27)
Endogenous guanidino compounds (GCs), nitrogen-containing metabolites, have very important physiological activities and participate in biochemical processes. Therefore, accurately characterizing the distribution of endogenous GCs and monitoring their concentration variations are of great significance. In this work, a new derivatization reagent, 4,4′-bis[3-(dimethylamino)propyl]benzyl (BDMAPB), with isotope-coded reagents was designed and synthesized for doubly charged labeling of GCs. BDMAPB-derivatized GCs not only promote the MS signal but also form multicharged quasimolecular ions and abundant fragment ions. With this reagent, an isotope-coded doubly charged labeling (ICDCL) strategy was developed for endogenous GCs with high-resolution liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF MS). The core of this methodology is a 4-fold multiplexed set of [d0]-/[d4]-/[d8]-/[d12]-BDMAPB that yields isotope-coded derivatized GCs. Following a methodological assessment, good linear responses in the range of 25 nM to 1 μM with correlation coefficients over 0.99 were achieved. The limit of detection and the limit of quantitation were below 5 and 25 nM, respectively. The intra- and interday precisions were less than 18%, and the accuracy was in the range of 77.3–122.0%. The percentage recovery in tissues was in the range of 85.1–113.7%. The results indicate that the developed method facilitates long-term testing and ensures accuracy and reliability. Finally, the method was applied for the simultaneous analysis of endogenous GCs in four types of lung tissues (solid adenocarcinoma, solid squamous-cell carcinoma, ground-glass carcinoma, and paracancerous tissues) for absolute quantification, nontargeted screening, and metabolic difference analysis. It is strongly believed that ICDCL combined with isotope-coded BDMAPB will benefit the analysis and study of endogenous GCs.
Nickel-catalyzed reductive monofluoroakylation of alkyl tosylate with bromofluoromethane to primary alkyl fluoride
Cui, Ru,Sheng, Jie,Wu, Bing-Bing,Hu, Duo-Duo,Zheng, Hong-Qian,Wang, Xi-Sheng
supporting information, p. 9084 - 9087 (2021/09/14)
A nickel-catalysed direct terminal monofluoromethlyation between alkyl tosylates and a low-cost, industrial raw material bromofluoromethane has been developed. This transformation has demonstrated high efficiency, mild conditions, and good functional-grou
Isolable Pyridinium Trifluoromethoxide Salt for Nucleophilic Trifluoromethoxylation
Duran-Camacho, Geraldo,Ferguson, Devin M.,Kampf, Jeff W.,Bland, Douglas C.,Sanford, Melanie S.
supporting information, p. 5138 - 5142 (2021/07/19)
An isolable pyridinium trifluoromethoxide salt is prepared from the reaction of 4-dimethylaminopyridine with the commercially available liquid 2,4-dinitro(trifluoromethoxy)benzene. The salt is an effective trifluoromethoxide source for SN2 reactions to form trifluoromethyl ethers.
Fluorination Triggers Fluoroalkylation: Nucleophilic Perfluoro-tert-butylation with 1,1-Dibromo-2,2-bis(trifluoromethyl)ethylene (DBBF) and CsF
Dong, Hui,Hu, Jinbo,Ni, Chuanfa,Tao, Quan,Wang, Qian,Xie, Xiaoming
supporting information, p. 27318 - 27323 (2021/11/22)
Perfluoro-tert-butylation reaction has long remained a challenging task. We now report the use of 1,1-dibromo-2,2-bis(trifluoromethyl)ethylene (DBBF) as a practical reagent for perfluoro-tert-butylation reactions for the first time. Through a consecutive triple-fluorination process with DBBF and CsF, the (CF3)3C? species can be liberated and observed, which is able to serve as a robust nucleophilic perfluoro-tert-butylating agent for various electrophiles. The power of this synthetic protocol is evidenced by the efficient synthesis of structurally diverse perfluoro-tert-butylated molecules. Multiple applications demonstrate the practicability of this method, as well as the superiority of perfluoro-tert-butylated compounds as sensitive probes. The perfluoro-tert-butylated product was successfully applied in 1H- and 19F-magnetic resonance imaging (MRI) experiment with an ultra-low field (ULF) MRI system.
Quaternary Ammonium Trifluoromethoxide Salts as Stable Sources of Nucleophilic OCF3
Britton, Robert,Friesen, Chadron M.,Jelier, Benson J.,Martin, Rainer E.,Meanwell, Michael,Newton, Josiah J.
, p. 1785 - 1790 (2020/03/24)
The reaction of nucleophilic tertiary amines with trifluoromethyl and pentafluoroethyl methyl ethers provides quaternary ammonium trifluoromethoxide (NR4OCF3) and pentafluoroethoxide (NR4OCF2CF3) salts, respectively, in good yields. The new trifluoromethoxide salts disclosed herein are uniquely stable for extended periods of time in both the solid state and in solution, which complements contemporary reagents. Here we describe the preparation of a range of NR4OCF3 salts, their long-term stability, and utility in substitution reactions.
Copper-Catalyzed Reductive Trifluoromethylation of Alkyl Iodides with Togni's Reagent
Chen, Yanchi,Ma, Guobin,Gong, Hegui
supporting information, p. 4677 - 4680 (2018/08/07)
This work illustrates a reductive cross-electrophile coupling protocol for trifluoromethylation of alkyl iodides under Cu-catalyzed/Ni-promoted reaction conditions. The use of diboron esters as the terminal reductant allows the effective generation of the alkyl-CF3 products with excellent functional group tolerance and broad substrate scope. A mechanism involving a reaction of alkyl-Cu with Togni's reagent was proposed.
