Synthesis of Sulfur-Containing Trisubstituted Imidazoles by One-Pot, Multicomponent Reaction via Electron Donor-Acceptor Complex Photoactivation.

Rapid and efficient construction of multifunctionalized skeletons through a one-pot multicompound domino reaction has been recognized as a simple and practical strategy. Herein, a visible-light-enabled three-component reaction of isothiocyanates, isocyanides, and thianthrenium salt-functionalized arenes is presented, which affords a facile approach to sulfur-containing trisubstituted imidazoles in good yields with a broad substrate scope and excellent functional group tolerance. The byproduct thianthrene is recovered in quantity, thereby ultimately reducing the production of chemical waste. The developed methodology has potential value for the discovery and development of thioimidazole-based drugs.

Arylthianthrenium Salts as the Aryl Sources: Visible Light/Copper Catalysis-Enabled Intermolecular Azidosulfonylation of Alkenes.

The difunctionalization of alkenes using aryl thianthrenium salts as the aryl sources has been reported sporadically. However, the four-component difunctionalization of alkenes on the basis of aryl thianthrenium salts has not been reported thus far and still remains a challenge. Herein, a visible light/copper catalysis-enabled four-component reaction of aryl thianthrenium salts, DABCO·(SO2)2, alkenes, and TMSN3 is presented, which affords a facile approach to ß-azidosulfones in good yields with broad substrate scope and excellent functional group tolerance. This strategy indirectly realizes the method for the synthesis of ß-azidosulfones through site-selective aryl C-H bond functionalization and alkene difunctionalization. This developed method is an important complement to thianthrenium salts chemistry.

Catalytic Enantioselective Primary C-H Borylation for Acyclic All-Carbon Quaternary Stereocenters.

Creating a perfect catalyst to operate enzyme-like chiral recognition has been a long-sought aim. A challenging example in this context is constructing acyclic all-carbon quaternary stereogenic centers by transition metal-catalyzed enantioselective C-H activation. We now report highly enantioselective iridium-catalyzed primary C-H borylation of α-all-carbon substituted 2,2-dimethyl amides enabled by a tailor-made chiral bidentate boryl ligand (CBL). The success of the current transformation is attributed to the CBL/iridium catalyst, which has a confined chiral pocket. This protocol provides a diverse array of acyclic all-carbon quaternary stereocenters with excellent enantiocontrol and distinct structural features. Computational study reveals that steric hindrance of CBL could regulate the type of dominant orbital interaction between the catalyst and substrate, which is crucial to conferring high chiral induction.

Towards outstanding lubricity performance of proton-type ionic liquids or synergistic effects with friction modifiers used as oil additives at the steel/steel interface.

Anti-wear (AW) additives and friction modifiers (FMs) and their interactions in lubricants are critical to tribological performance. This research investigates the compatibility and synergism of three oil-soluble alkylamine-phosphate ionic liquids with friction modifiers, organomolybdenum compounds. Three proton-based ionic liquids (PILs) were synthesized using a simple, low-cost, and unadulterated procedure as well as the chain lengths of the PILs affected the effectiveness of friction reduction and anti-wear. For example, the effect of a short-chain PIL alone as an additive on friction and wear behavior was not significant, whereas a long-chain PIL was more effective. In addition, PILs appeared to be able to coexist with organic molybdenum compounds and worked synergistically with dialkyl dithiophosphate oxygen molybdenum (MoDDP) to produce a sustained low coefficient of boundary friction (the coefficient of friction approaching 0.042). We proposed a three-stage tribochemical process to explain this interaction of PILs + MoDDP with contact surfaces to form physically adsorbed friction-reducing films and chemically reactive wear-protective films. This study reveals the compatibility and synergistic effects of two common lubricant components, which can be used to guide lubricant development in the future.

Effect of the Ruan Jian Qing Mai Recipe on Wound Healing in Diabetic Mice and Prediction of its Potential Targets.

BACKGROUND: The "Ruan Jian Qing Mai (RJQM) recipe" is a traditional Chinese medicine (TCM), which has been found to have significant curative effects on diabetic ulcers in the clinic for a long time. Previous research has shown that RJQM can improve diabetic skin wound healing and promote angiogenesis. However, the active ingredients of the RJQM recipe and its pharmacological mechanism of treatment for diabetic skin wound healing still remain unclear.This study aims to investigate the effect of the RJQM recipe on diabetic wound healing, and to identify the possible active ingredients and their mechanism. METHODS: First, a skin injury model was established in diabetic mice, and wound healing was evaluated by hematoxylin-eosin (HE) staining, quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and western blot analysis. Second, the chemical constituents of the RJQM recipe were analyzed and identified by ultra pressure liquid chromatography-mass spectrometry (UPLC-MS). Finally, the possible targets of drug treatment for diabetic skin injury were analyzed by network pharmacology and verified by in vitro experiments using cell culture. RESULTS: (1) In the full-thickness skin injury model, the skin wound healing rate and healing area were significantly increased in mice treated with the RJQM recipe compared with those of the model group. The results of immunofluorescence staining showed that the RJQM recipe could increase the expression of VEGF protein and promote the proliferation of vascular smooth muscle cells and the formation of microvessels, and RT-qPCR results found that the mRNA expression of angiogenesis-related factors in the RJQM recipe group was significantly higher than that in the model group. (2) A total of 25 compounds were identified by UPLC-MS. (3) According to the results of network pharmacology, the therapeutic effect of the RJQM recipe on diabetic skin injury may be related to S6 (quercetin), S1 (typhaneoside), S18 (isoliquiritigenin), protein kinase B-α (Akt1), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), insulin-like growth factor I receptor (IGF1R), vascular endothelial growth factor-a (VEGF-a), signal transducer and activator of transcription-3 (STAT3) and phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathways. Based on the predictions by network pharmacology, we proved that the drug could treat diabetic skin damage by activating the PI3K-Akt-VEGF signaling pathway. CONCLUSION: The RJQM recipe promotes the formation of granulation tissue during the process of wound healing and exerts a good therapeutic effect on diabetic skin wound healing.

Discovery of a Novel Potent Antitumor Molecule, P19G1, by Erlotinib Derivative Libraries Synthesized by Modular Click-Chemistry.

Objective:Traditional chemical synthesis methods are cumbersome and inefficient. In this study, a novel antitumor molecule, 4-(4-(3-((6,7-bis(2-methoxyethoxy)quinazolin-4-yl)amino)phenyl)-1H-1,2,3-triazol-1-yl)phenyl sulfurofluoridate (P19G1), was identified by screening a library of Erlotinib derivatives synthesized by modular click chemistry, and the antitumor activity and underlying mechanism of P19G1 were further revealed. Methods: A series of Erlotinib derivatives (840 compounds) were synthesized using a modular click-chemistry method, and then the thiazolyl blue (MTT) method was used to screen and evaluate the inhibitory effect of these compounds on the growth and metastasis of A549 lung adenocarcinoma cells. Among them, the compound P19G1 showed the best inhibitory activity. Furthermore, the antitumor activity and mechanism of P19G1 were investigated with in vitro cell biology and in vivo assays in an animal model. Results: In vitro pharmacological studies showed that P19G1 had inhibitory effects on a variety of tumor cell lines with IC50 values in the range of 1 to 5 µM. Moreover, P19G1 significantly inhibited the proliferation and migration of the human lung adenocarcinoma cell line A549 and human colorectal cancer cell line RKO and promoted cell apoptosis. In vivo tumor-bearing mouse model experiments revealed that 50 mg/kg P19G1 effectively inhibited the growth and metastasis of A549 tumors without obvious toxicity to the host. Conclusions: The rapid structural modification of lead compounds using novel modular click-chemistry reactions holds great potential for use in obtaining diverse derivatives for tumor drug screening and development. P19G1 was discovered because of the application of click chemistry in this study, and it is an antitumor candidate molecule worthy of development.

Iridium-Catalyzed Enantioselective C(sp3 )-H Borylation of Aminocyclopropanes.

Transition-metal-catalyzed regio- and stereo-controllable C-H functionalization remains a formidable challenge in asymmetric catalysis. Herein, we disclose the first example of iridium-catalyzed C(sp3 )-H borylation of aminocyclopropanes by using simple imides as weakly coordinating directing groups under mild reaction conditions. The reaction proceeded via a six-membered iridacycle, affording a vast range of chiral aminocyclopropyl boronates. The current method features a broad spectrum of functional groups (36 examples) and high enantioselectivities (up to 99 %). We also demonstrated the synthetic utility by a preparative scale C-H borylation, C-B bond transformations, and conversion of the directing group.

Chiral Bidentate Boryl Ligand Enabled Iridium-Catalyzed Enantioselective C(sp3)-H Borylation of Cyclopropanes.

We herein report an Ir-catalyzed enantioselective C(sp3)-H borylation of cyclopropanecarboxamides using a chiral bidentate boryl ligand for the first time. A variety of substrates with α-quaternary carbon centers could be compatible in this reaction to provide ß-borylated products with good to excellent enantioselectivities. We have also demonstrated that the borylated products can be used as versatile precursors engaging in stereospecific transformations of C-B bonds, including the synthesis of a bioactive compound Levomilnacipran.

NHC-Copper-Catalyzed Asymmetric Dearomative Silylation of Indoles.

We report an asymmetric dearomative silylation reaction of 3-acylindoles using a chiral NHC-copper(I) complex as catalyst to afford a range of cyclic α-aminosilanes with high regio- and enantioselectivity. Initial mechanistic studies revealed that the observed high diastereoselectivity was attributed to the facile epimerization of the 3-acyl group. We also demonstrated that the product could be used as a versatile precursor for the synthesis of functionalized indolines in high enantiomeric purity.