Metal-Free Cyanation of gem-Difluoroalkenes via Azide-Mediated C-C Double Bond Fragmentation.

Activation and cleavage of C-C double bonds are long-standing challenges in synthetic chemistry. Herein, we report an unprecedented azide-mediated C-C double bond fragmentation of gem-difluoroalkenes under mild and metal-free conditions, enabling the efficient synthesis of structurally diverse aromatic nitriles in moderate to good yields. This protocol is also amenable to the cyanation of gem-dichloro and dibromo alkenes. This reaction features simple operation and good functional group compatibility and can be implemented at a gram scale.

Selective S-arylation of thiols with o-OTf-substituted diaryliodonium salts toward diarylsulfides.

In contrast to the previously reported intramolecular aryl migration, we present the selective sulfenylation of ortho-trifluoromethanesulfonate (OTf) substituted diaryliodonium salts with thiols. As such, diarylsulfides bearing vicinal OTf groups were synthesized in good yields. The unique reactivity of the vicinal OTf group and the sulfur atom in arylsulfides offers further transformations.

Luteolin: A promising multifunctional natural flavonoid for human diseases.

Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti-convulsion, diabetes control, anti-inflammatory, neuroprotection, anti-oxidation, anti-cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF-κB, toll-like receptor, MAPK, Wnt/ß-catenin, PI3K/Akt, AMPK/mTOR, and Nrf-2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT.

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins.

Cyclic annulation involving diaryliodonium salts is an efficient tool for the construction of two or more chemical bonds in a one-pot process. Ortho-functionalized diaryliodonium salts have showcased distinct reactivity in the exploration of benzocyclization or arylocyclization. With this strategy of ortho-ester-substituted diaryliodonium salts, herein, we utilized a copper catalyst to activate the C-I bond of diaryliodonium salts in the generation of aryl radicals, thus resulting in an annulation reaction with naphthols and substituted phenols. This approach yielded a diverse array of 3,4-benzocoumarin derivatives bearing various substituents.

Ultra-Strong Comprehensive Radiation Effect Tolerance in Carbon Nanotube Electronics.

Carbon nanotube (CNT) field-effect transistors (FETs) have been considered ideal building blocks for radiation-hard integrated circuits (ICs), the demand for which is exponentially growing, especially in outer space exploration and the nuclear industry. Many studies on the radiation tolerance of CNT-based electronics have focused on the total ionizing dose (TID) effect, while few works have considered the single event effects (SEEs) and displacement damage (DD) effect, which are more difficult to measure but may be more important in practical applications. Measurements of the SEEs and DD effect of CNT FETs and ICs are first executed and then presented a comprehensive radiation effect analysis of CNT electronics. The CNT ICs without special irradiation reinforcement technology exhibit a comprehensive radiation tolerance, including a 1 × 104 MeVcm2 mg-1 level of the laser-equivalent threshold linear energy transfer (LET) for SEEs, 2.8 × 1013 MeV g-1 for DD and 2 Mrad (Si) for TID, which are at least four times higher than those in conventional radiation-hardened ICs. The ultrahigh intrinsic comprehensive radiation tolerance will promote the applications of CNT ICs in high-energy solar and cosmic radiation environments.

Diaryliodonium Salts Enabled Arylation, Arylocyclization, and Aryl-Migration.

Our research interest focusing on synthetic methodology with diaryliodonium salts, is summarized in this account. Besides employing a dual activation strategy of C-I and ortho C-H bonds, we have introduced vicinal functional groups at ortho-positions of diaryliodonium salts, in which their unique reactivities have been explored in various processes, including arylation, diarylation, cascade annulation, benzocyclization, arylocyclization, and intramolecular aryl migration. The variety of mechanisms of these reactions that involves either transition metals, especially palladium in organometallic catalysis, or transition-metal free conditions, were discussed in the context.

Diversification of Complex Diaryl Ethers via Diaryliodonium Intramolecular Aryl Rearrangement.

In this study, we present an efficient site-selective O-arylation method applicable to a broad range of complex arenes involving intramolecular aryl rearrangement. The reaction was facilitated by diaryliodonium salts bearing vicinal trifluoromethanesulfonate (OTf) groups. The procedure was initiated with selective C-H bond activation of arenes, which were then converted into diaryl ethers through nucleophilic aromatic substitution (SNAr). This synthetic method successfully affords complex diaryl ether derivatives, showcasing its practicality for the diversification of functionalized arenes and pharmaceutical agents.

Truce-Smiles Rearrangement of Diaryliodonium Salts in Ionic Liquids.

The Truce-Smiles rearrangement is an intramolecular SN Ar reaction, enabling the formation of a new arene carbon-carbon bond with sufficiently strong carbon-centered nucleophile. Reported here are ortho-tosylmethylene functionalized diaryliodonium salts, which can undergo an unprecedented Truce-Smiles rearrangement in ionic liquids, resulting in sulfonyl-substituted ortho-iodo diarylmethanes as a powerful class of building blocks in chemical synthesis. The protocol features aryliodo moiety as a hyper nucleofuge, facilitating the formation of Meisenheimer complex within the migratory system.

ortho-Nitro-substituted diaryliodonium salts enabled regioselective cyclization of arylcarboxylic acids toward 3,4-naphthocoumarins.

We herein report an efficient regioselective cascade of arylation and cyclization of arylcarboxylic acids via Pd(II)-activation of both C-I and vicinal C-NO2 bonds of ortho-nitro-substituted diaryliodonium salts.

Pterostilbene nanoparticles with small particle size show excellent anti-breast cancer activityin vitroandin vivo.

Pterostilbene (PTE) is known as resveratrol of the next generation and it has attracted extensive attention in recent years. PTE can inhibit the growth of a variety of tumor cells. To overcome the problem of insolubility, PTE was loaded into nanoparticles (NPs) by anti-solvent precipitation technique using soybean lecithin (SPC) and D-α-tocopheryl polyethylene glycol succinate (TPGS) as stabilizers. The obtained PTE-NPs had an average particle size of 71.0 nm, a polydispersity index （PDI） value of 0.258, and a high zeta potential of -40.8 mV. PTE-NPs can maintain particle size stability in various physiological media. The entrapment efficiency of PTE-NPs was 98.24%. And the apparently water solubility of PTE-NPs was about 53 times higher than the solubility of PTE (54.41µg ml-1v-1s-1. 2.89 mg ml-1). M-1T-1T-1assay showed that the antitumor activity of PTE-NPs on 4T1 breast cancer cells, MCF-7 breast cancer cells and Hela cervical cancer cells was significantly increased by 4, 6 and 8 times than that of free PTE, respectively.In vivostudies have shown that PTE-NPs has a certain dose dependence. When injected intraperitoneally, PTE-NPs showed a similar therapeutic effect as paclitaxel injection (TIR was 57.53% versus 57.23%) against 4T1 tumor-bearing mice. This should be due to the improved bioavailability of the drug caused by nano-drug delivery system (nano-DDS). These results indicate that PTE-NPs may be a clinically promising anti-tumor drug for breast cancer treatment.

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen.

BACKGROUND: Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class. METHODS: Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset. RESULTS: A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion. CONCLUSIONS: Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.

Palladium-Catalyzed Site-Selective Benzocyclization of Naphthoic Acids with Diaryliodonium Salts: Efficient Access to Benzanthrones.

Dual activation of both C-I and vicinal C-H bonds of diaryliodonium salts allowing for diarylation is a subject of rapid construction of π-extended frameworks. Here, we report palladium-catalyzed cascade of C8-arylation/intramolecular Friedel-Crafts acylation of α-naphthoic acids in the synthesis of benzanthrone derivatives. The step-economical protocol tolerates various substrates, which resulted in a potential molecular library for developing functional polycyclic scaffolds. The approach relies on the synergistic action of strong acid with palladium catalysts to form two bonds in a one-pot procedure.

Hypervalent Iodine(III)-Mediated Tosyloxylation of 4-Hydroxycoumarins.

An efficient approach was developed for synthesis of 3-tosyloxy-4-hydroxycoumarins under mild conditions by using Koser's reagents. The reaction tolerated various functional groups, and the products served as useful aromatic building blocks. Additionally, a plausible mechanism via iodonium ylide was proposed, and the oral anticoagulant Warfarin was synthesized in good yield.

Palladium Catalyzed C-I and Vicinal C-H Dual Activation of Diaryliodonium Salts for Diarylations: Synthesis of Triphenylenes.

Using the synthetic strategy of palladium-catalyzed dual activation of both C-I and vicinal C-H bonds of diaryliodonium salts, we report an approach for direct diarylations of 2-bromobiphenyls or bromobenzenes. As a result, a wide range of triphenylenes with various substituents have been synthesized in good yields. These triphenylenes are expected to be employed in the "bottom-up" synthesis of functional aromatic molecules in material science.

Two new daphnane diterpenes from the roots of Stelleropsis tianschanica.

Two new daphnane diterpenes named tianchaterpenes A and B were isolated from the roots of Stelleropsis tianschanica. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS. Compounds 1 and 2 were evaluated for their cytotoxic activities against HeLa and HCT-8 cell lines. The results showed that all compounds displayed weak cytotoxicities to the HeLa cells and were inactive to the HCT-8 cells.

Intramolecular Aryl Migration of Diaryliodonium Salts: Access to ortho-Iodo Diaryl Ethers.

By using vicinal trifluoromethanesulfonate-substituted diaryliodonium salts, a novel approach was developed for the synthesis of ortho-iodo diaryl ethers by intramolecular aryl migration. The reaction conditions are mild with a broad substrate scope. Mechanistic insight suggests a sulfonyl-directed nucleophilic aromatic substitution pathway. Additionally, the product ortho-iodo diaryl ethers serve as versatile synthons as demonstrated with several coupling reactions. Furthermore, a useful thyroxine analogue of the 3-iodo-l-thyronine (3-T1 ) derivative was synthesized by this aryl migration procedure.

Diels-Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts.

With a strategy of the formation of benzynes by using diaryliodonium salts, a cycloaddition reaction of N-arylpyrroles with benzynes was reported. A wide range of bridge-ring amines with various substituents have been synthesized in moderate to excellent yields (35-96%). Furthermore, with a catalytic amount of TsOH·H2O, these amines can be converted into the corresponding N-phenylamine derivatives easily, which are potentially useful in photosensitive dyes.

Asymmetric Darzens Reaction of Isatins with Diazoacetamides Catalyzed by Chiral BINOL-Titanium Complex.

An efficient catalytic asymmetric Darzens reaction of N-protected isatins with diazoacetamides using a chiral BINOL/Ti(OiPr)4 complex as the catalyst has been developed. This reaction is a straightforward method for the synthesis of spiro-epoxyoxindoles in 40-95% yields, up to >20:1 dr and up to >99% ee. A gram-scale reaction was also achieved in 95% yield with excellent stereoselectivity and enantioselectivity (>20:1 dr, >99% ee).

Synthesis of 2,3-Disubstituted NH Indoles via Rhodium(III)-Catalyzed C-H Activation of Arylnitrones and Coupling with Diazo Compounds.

A rhodium-catalyzed intermolecular coupling between arylnitrones and diazo compounds by C-H activation/[4 + 1] annulation with a C(N2)-C(acyl) bond cleavage is reported, and 2,3-disubstituted NH indoles are directly synthesized in up to a 94% yield. A variety of functional groups are applicable to this reaction to give the corresponding products with high selectivity. Compared to other previously reported Rh(III)-catalyzed synthesis of homologous series, this method is simpler, more general, and more efficient.

Palladium-Catalyzed Double-Suzuki-Miyaura Reactions Using Cyclic Dibenziodoniums: Synthesis of o-Tetraaryls.

Palladium-catalyzed double-Suzuki-Miyaura couplings between cyclic dibenziodoniums and arylboronic acids have been developed. As such, a wide range of o-tetraaryls were synthesized in good to excellent yields of 22-94%. Furthermore, tetraphenylene was prepared in 21% isolated yield with 2,2'-biphenyldiboronic acid by using this method.