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The preparation of unsaturated secondary lactams via the palladium-catalyzed cyclization of O-phenyl hydroxamates onto a pendent alkene is reported. This method provides rapid access to a broad range of lactams that are widely useful building blocks in alkaloid synthesis. Mechanistic studies support an aza-Heck-type pathway.

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Metal catalyst and ligand design,
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(Matrix presented) This report details the kinetic responses of nine compounds of type 6 to ring-closing metathesis as promoted by 2 to give the identical product 7. The experimental observations have been subjected to Hammett analysis. The rho value for the composite aromatic derivatives (R = p-XC6H4-) differs from that of the aliphatic series, although both are negative because electron-donating groups accelerate the reaction.

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The first family of extended and fluorinated corannulenes is prepared through a highly efficient and modular synthetic strategy. In this strategy, corannulene aldehyde could be combined with the fluorine-carrying phosphonium ylides to furnish stilbene-like vinylene precursors. A photochemically induced oxidative cyclization process of these precursors gives rise to the fluorinated and curved polycyclic aromatic hydrocarbons. A UV-vis absorption study shows that aromatic extension results in a bathochromic shift of about 12 nm. Fluorination further shifts the absorption spectrum to the red region, and a maximum shift of about 22 nm is detected for a compound carrying two trifluoromethyl groups. A cyclic and square-wave voltammetry investigation reveals that the extension of the corannulene scaffold increases the reduction potential by 0.11 V. Placement of fluorine or trifluoromethyl groups further enhances the electron affinities. In this regard, the presence of one trifluoromethyl group equals the effect of three aromatic fluorine atoms. Molecules with two trifluoromethyl groups, meanwhile, exhibit the highest reduction potentials of -1.93 and -1.83 V. These values are 0.37 and 0.46 V higher than those of the parental corannulene and demonstrate the utility of the present design concept by efficiently accessing effective electron acceptors based on the buckybowl motif.

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Metal catalyst and ligand design,
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Liver X receptor (LXR) agonists are candidates for the treatment of atherosclerosis via induction of ABCA1 (ATP-binding cassette A1) gene expression, which contributes to reverse cholesterol transport (RCT) and to cholesterol efflux from the liver and intestine. However, LXR agonists also induce genes involved in lipogenesis, such as SREBP-1c (sterol regulatory binding element protein 1c) and FAS (fatty acid synthase), thereby causing an undesirable increase in plasma and hepatic triglyceride (TG) levels. Recent studies indicate that LXRalpha contributes to lipogenesis in liver, and selective LXRbeta activation improves RCT in mice. Therefore, LXRbeta-selective agonists are promising candidates to improve atherosclerosis without increasing plasma or hepatic TG levels. However, the ligand-binding domains in the two LXR isoforms alpha/beta share high sequence identity, and few LXR ligands show subtype selectivity. In this study we identified a tetrachlorophthalimide analogue as an LXRbeta-selective agonist. Structural development led to (E)-4,5,6,7-tetrachloro-2-(2-styrylphenyl)isoindoline-1,3-dione (24 a), which shows potent and selective LXRbeta agonistic activity in reporter gene assays. In binding assays, compound 24 a bound to LXRbeta preferentially over LXRalpha. It also induced the expression of ABCA1 mRNA but not SREBP-1c mRNA in cells. Compound 24 a appears to be a promising lead compound for therapeutic agents to treat atherosclerosis without the side effects induced by LXRalpha/beta dual agonists.

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Metal catalyst and ligand design,
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In our ongoing exploration of the structure-activity landscape of anti-invasive chalcones, we have prepared and evaluated a number of structurally related (E)- and (Z)-stilbenes. These molecules exhibited an extraordinary high in vitro potency in the chick heart invasion assay, being active up to 10 nmol L-1, a concentration level a 100-fold lower than the lowest effective doses that have been reported for natural analogues. Furthermore, they possess an interesting pharmacological profile in silico.

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Metal catalyst and ligand design,
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A covalent dyad was synthesized in which perylene-3,4,:9:10-bis(dicarboximide) (PDI) is linked to beta-apocarotene (Car) using a biphenyl spacer. The dyad is monomeric in toluene and forms a solution aggregate in methylcyclohexane (MCH). Using femtosecond transient absorption (fsTA) spectroscopy, the monomeric dyad and its aggregates were studied both in solution and in thin films. In toluene, photoexcitation at 530 nm preferentially excites PDI, and the dyad undergoes charge separation in tau = 1.7 ps and recombination in tau = 1.6 ns. In MCH and in thin solid films, 530 nm excitation of the PDI-Car aggregate also results in charge transfer that competes with energy transfer from 1 PDI to Car and with an additional process, rapid Car triplet formation in <50 ps. Car triplet formation is only observed in the aggregated PDI-Car dyad and is attributed to singlet exciton fission (SF) within the aggregated PDI, followed by rapid triplet energy transfer from 3PDI to the carotenoid. SF from beta-apocarotene aggregation is ruled out by direct excitation of Car films at 414 nm, where no triplet formation is observed. Time-resolved electron paramagnetic resonance measurements on aggregated PDI-Car show the formation of 3Car with a spin-polarization pattern that rules out radical-pair intersystem crossing as the mechanism of triplet formation as well. A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 4062-60-6 Reference:
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Microtubule-targeting agents (MTA) have enjoyed significant clinical success for decades. However, several mechanisms may cause inactivation of such drugs, leading to acquired resistance in patients treated with them. Therefore, drugs containing a stilbene-like skeleton and possessing dual inhibitory activity may provide a new and differentiated treatment for patients to overcome challenging acquired resistance. A new compound (16c) displays promising anticancer activity with GI50 of 22 ± 2 and 12 ± 0.1 nM in vincristine-resistant nasopharyngeal (KB-Vin) cancer cells and etoposide-resistant nasopharyngeal (KB-7D) cancer cells and is better than vincristine, etoposide, ABT-751, and MS-275. A mechanistic study revealed that 16c interferes with the cell cycle distribution and induces cell cycle arrest at the G2/M phase and severe mitotic spindle defects followed by apoptosis. In addition, it produces much more significant cytotoxicity than vincristine and etoposide in the corresponding resistant cells, indicating that it may be a promising candidate to overcome drug resistance in cancer cells. Compound 16c also displays inhibitory activity against HDAC 1 and HDAC 2 with IC50 values of 1.07 muM, and 1.47 muM, respectively. These findings may lead to a new type of structural motif for future development of drugs that could overcome acquired resistance to MTAs.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The unique nature of the alumina-mediated cyclodehydrofluorination gives the opportunity to execute the preprogrammed algorithm of the C?C couplings rationally built into a precursor. Such multi-assemblies facilitate the construction of the carbon-skeleton, superseding the conventional step-by-step by the one-pot intramolecular assembly. In this work, the feasibility of the alumina-mediated C?F bond activation approach for multi-assembly is demonstrated on the example of a fundamental bowl-shaped polycyclic aromatic hydrocarbon (diindenochrysene) through the formation of all ?missing? C?C bonds at the last step. Beside valuable insights into the reaction mechanism and the design of the precursors, a facile pathway enabling the two-step synthesis of diindenochrysene was elaborated, in which five C?C bonds form in a single synthetic step. It is shown that the relative positions of fluorine atoms play a crucial role in the outcome of the assembly and that governing the substituent positions enables the design of effective precursor molecules ?programmed? for the consecutive C?C bond formations. In general, these findings push the state of the field towards the facile synthesis of sophisticated bowl-shaped carbon-based nanostructures through multi-assembly of fluoroarenes.

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Metal catalyst and ligand design,
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Kinetics and linear free energy relationship (LFER) of Wittig reaction of ylides of intermediary stability have been investigated.Evidences are presented which indicate that under such cases the reaction follows a second order rate law, first order in phosphorane and aldehyde respectively, and furthermore that electron withdrawing substituents on both benzaldehyde and benzylidenetriphenylphosphorane impose rate enhancement effect upon the reaction.The mechanism of the reaction is discussed on the basis of the experimental findings

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2-Phenylselanyl-1,3-dienes 3-8 were prepared by a Wittig or Wittig-Horner-Emmons procedure starting from alpha-phenylselanyl alpha,beta-unsaturated aldehydes. Ratio and configuration of each diene isomers were determined by 77Se and 1H NMR. These dienes were then oxidized into selenoxides, which could be isolated in some cases. In THF, [2,3]-sigmatropic rearrangement of allylic selenoxides, selenimides, and dihalo-selenuranes occurred, yielding allenyl alcohols 12-15, allenyl carbamates 16c-19c, and 1-haloalkyl allenes 20c-22c, respectively.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI