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Synthesis, structure determination and in vitro antiproliferative assay of a series of novel ferrocenenyl hydrazones containing 4-halopyridazin-3(2H)-one fragment(s) and three representative N-arylsubstituted (Sp)-ferroceno[d] pyridazinones are presented. The model compounds can be considered as different assemblies of the potential binding sites capable of establishing interactions including hydrogen bonds and pi-pi interactions with the relevant residues of biomolecules. Their in vitro antiproliferative effect was investigated against four tumorous cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT)-assay. Our data indicate that bis-hydrazone of 1,1?-diformylferrocene carrying N-benzyl substituents and a chloropyridazinyl-substituted ferroceno[d]pyridazinone display significant activity on each cell lines investigated. The efficiency of the latter drug candidate and one N-benzyl mono-hydrazone on A2870 cell line is comparable to that of cisplatin. The constitution and relative configuration of the model compounds were established by 1H, 13C and 15N NMR methods. The structures of a mono- and bis-ferrocenylhydrazone containing 4-bromopyridazinone unit(s) were confirmed by single crystal X-ray diffraction.

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Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Condensation reaction of 1,1?-ferrocenedicarboxaldehyde with (1R,2R)-1,2-diaminocydohexane affords a novel bowl-shaped macrocycle with a chiral concave cavity which exhibits a remarkable ability as a host material for the enantioselective enclathration of 1,1?-bi-2-naphthol.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Readily available alpha-amino aldehydes, incorporating a methylthiomethyl (MTM) protecting group on nitrogen, are shown to be efficient substrates in Rh-catalyzed alkyne hydroacylation reactions. The reactions are performed under mild conditions, employing a small-bite-angle bis-phosphine ligand, allowing for good functional group tolerance with high stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched alpha-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the alpha-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.

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Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Understanding the mechanism of action (MOA) of bioactive natural products will guide endeavor to improve their cellular activities. Artemisinin and its derivatives inhibit cancer cell proliferation, yet with much lower efficiencies than their roles in killing malaria parasites. To improve their efficacies on cancer cells, we studied the MOA of artemisinin using chemical proteomics and found that free heme could directly activate artemisinin. We then designed and synthesized a derivative, ART-TPP, which is capable of targeting the drug to mitochondria where free heme is synthesized. Remarkably, ART-TPP exerted more potent inhibition than its parent compound to cancer cells. A clickable probe ART-TPP-Alk was also employed to confirm that the attachment of the TPP group could label more mitochondrial proteins than that for the ART derivative without TPP (AP1). This work shows the importance of MOA study, which enables us to optimize the design of natural drug analogues to improve their biological activities.

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Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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The present invention discloses a synthetic alpha- the alkyl is fragrant acetamide method. In the reaction container, adding fragrant second grade nitrile, the compound is mellow, a transition metal catalyst complex of metal, alkali, and an organic solvent to the metallisation; or the microwave reactor the reaction mixture under stirring with magnetic force, 130 C after the reaction, cooling to room temperature, then through the column separation, to obtain a target compound. From nitrile and mellow of the present invention as a starting material, in the transition metal catalyst, with the participation of the metallisation and alkali, direct synthesis of alpha-alkyl benzene acetamide, reaction exhibit three significant advantages: 1) the use of commercial or easily prepared nitrile and almost non-toxic alcohol as the starting material; 2) reaction atom economy is high; therefore, the reaction in accordance with the requirement of green chemistry, has broad prospects of development. (by machine translation)

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Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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The trifluoromethylcarbene (:CHCF3) was found to be conveniently generated from (2,2,2-trifluoroethyl)diphenyl-sulfonium triflate (Ph2S+CH2CF3 -OTf), which was successfully applied in Fe-catalyzed cyclopropanation of olefins, giving the corresponding trifluoromethylated cyclopropanes in high yields.

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Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Reaction of ferrocenecarbothioamide and N-(ethoxycarbonyl)ferrocenecarbothioamide with alkyl (mainly benzyl) halides in the presence of K2CO3 has been studied. The former compound yielded cyanoferrocene in high yield whereas the latter was transformed into the corresponding thioimidates as a result of S-alkylation and deprotonation. The molecular structure of S-p-nitrobenzyl-N-(ethoxycarbonyl)-ferrocenethioimidate was determined by single-crystal X-ray analysis and revealed the E configuration. The plausible reaction mechanism is discussed.

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Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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A series of enantioenriched ferrocenyl monophosphines imbued with both central and planar chirality were obtained catalytically (80?99% ee) via the kinetic resolution of 1,2-disubstituted planar chiral ferrocenyl enone racemates. The synthetic approach utilized a chiral palladacycle to facilitate the asymmetric hydrophosphination (AHP) as a means to achieve high stereoselectivity. The enantioenriched ferrocenylphosphine products could be protected and further recrystallized to obtain ees up to 99%. The modularity of the phosphine framework obtained was demonstrated via derivatization of its functional handles via a simple nucleophilic substitution to yield optically pure bisphosphines.

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Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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A has cytotoxicity to tumor targeting effects of ferrocene base Uygur formic acid/paclitaxel nano particle and its in the preparation of medicament for treating tumor application, belongs to the technical field of medicament. The invention preparation of nano particle retains the tretinoin inhibiting tumor stem cell proliferation, inducing activity, taxol can be carried at the same time the role of anti-personnel tumor stem cell outside of the common tumor cells; and the nano-particles to a tumor cell in a high concentration of reduced glutathione sensitive, into tumor cells can be rapidly cleavage after the release of the paclitaxel, exposed tretinoin functional group, their role; in the normal cell because less reductive glutathione content, will not be released or very few release, to reduce the toxic effect of the normal cells. At the same time, the nano-particle portable and transfer Micro – RNA into a cell to play a relevant role in, thus can be used for preparing medicaments for treating tumors. (by machine translation)

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Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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The synthesis and characterisation of a series of ferrocenylaminoalcohols is reported. 1,2-Aminoalcohol compounds were prepared from the respective ferrocene aldehydes via reaction with trimethylsilylcyanide followed by reduction with LiAlH4. This series includes the ferrocene derivative 1,1?-dimethyl-3-(2-amino-1-hydroxyethyl)ferrocene 1, which is used as a redox mediator to glucose oxidase in a commercial biosensor for determining blood glucose levels in diabetics. The aminoalcohol derivatives are included in a structure-activity study involving the electrochemical determination of the mediation rates of a range of systematically substituted ferrocenes with glucose oxidase. These mediation rates are correlated with structure.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion