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A process for the synthesis of C7-functionalized indoles using para-substituted 2-alkynylanilines as starting materials was reported. The process involves a dearomatization, an 1,2-addition by organic lithium or Grignard reagents, an aromatization-driven allylic rearrangement, and a cyclization. A variety of groups including alkyl, aryl, alkenyl, or alkynyl groups were selectively installed at the C7 site of indoles leading to the formation of 2,5,7-trisubstituted indoles.

A dearomatization method for divergent synthesis of 4-amino indoles having N1 or C4 free amine groups from 2-alkynylanilines was reported.

A method for stereoselective construction of acyclic all-carbon tetrasubstituted alkenes through insertion of nitrile-substituted trimethylenemethane into the aryl C-N bond in anilines via an aromaticity destruction-reconstruction process is reported. The process involves dearomatization, azo-[3 + 2] TMM cycloaddition and aromatization-triggered rearrangement.

An anodic oxidative dearomatization reaction of 2-alkynylanilines was developed. The formed dearomatized compounds were used as versatile precursors in the synthesis of a variety of benzenoid ring multi-functionalized indoles through simple conversions.

A one-pot stepwise procedure for the synthesis of N-indolated amino acids or peptides from readily available 2-alkynylanilines was reported. The protocol involves the oxidative dearomatization of 2-alkynylanilines, the imino exchange with aliphatic amines, and subsequent cascade cyclization/nucleophilic addition/aromatization. The synthetic method might allow a rapid access to indolactam alkaloid derivatives.

A nitrogen replacement process that directly incorporates the 15N atom of glycine-15N into anilines was reported. The process involves a Csp2–N bond cleavage of anilines driven by dearomatization and a Csp3–N bond cleavage of glycine-15N driven by aromatization. A variety of 15N-labeled aromatic heterocycles can be prepared via this process.

A process for rapid synthesis of 4-acetoxyindoles from readily available 2-alkynylanilines was reported. The process involves an oxidative dearomatization and subsequent cascade nucleophilic addition/cyclization/aromatization. A range of functional groups can be tolerated in this process. The formed 4-acetoxyindoles are versatile precursors to a variety of C4-functionalized indoles through simple conversions.

An iodobenzene-catalyzed oxidative cyclization of Michael adducts of activated methylene compounds with nitroolefins or chalcones is developed. mCPBA is used as oxidant together with Bu4NI for the generation of a highly reactive iodine(III) species to mediate the cyclopropanation via a ligand exchange and reductive elimination process. A range of highly functionalized cyclopropanes are synthesized with high diastereoselectivities.

A process that rapidly assembles 4,7-difunctionalized indoles from 2-alkynycyclohexadienimines, sulfinamides, and nucleophiles (amines or alcohols) was developed. The process involves imino exchange, cascade cyclization/1,4-nucleophilic addition/aromatization, and 1,3-migration of the sulfinyl group. The 7-sulfinyl group is easy to convert into the sulfonyl or the thioether group through a simple oxidation and reduction reaction.

A nitrogen replacement process that directly incorporates the 15N atom of glycine-15N into anilines was reported. The process involves a Csp2-N bond cleavage of anilines driven by dearomatization and a Csp3-N bond cleavage of glycine-15N driven by aromatization. A variety of 15N-labeled aromatic heterocycles can be prepared via this process.

A simple method for rapid synthesis of 4-alkylindoles from 2-alkynylanilines was reported. The protocol involves an oxidative dearomatization and an aromatization triggered regioselective alkyl migration. A range of alkyl groups including linear, branched, or cycloalkyl groups can be introduced into the C4 position of indole.

Insertion of atoms into aromatic carbon-nitrogen bonds is an appealing method for the synthesis of nitrogen-containing molecules and it has the advantage of the availability and abundance of anilines. However, the direct cleavage of aromatic carbon-nitrogen bonds is challenging due to the particularly inert and stable nature of these bonds. Here we report a formal, enantioselective one-carbon insertion into an aromatic carbon-nitrogen bond via an aromaticity dissembly-reconstruction process to directly convert anilines to chiral α-branched benzylic amines. The process involves oxidative dearomatization of para-substituted anilines, chiral sulfur ylide-mediated asymmetric aziridination, and subsequent rearrangement. Chiral sulfur ylides serve as one-carbon insertion units., Atom insertion into aromatic carbon-nitrogen (C-N) bonds is useful for the synthesis of nitrogen-containing molecules, but challenging due to the inert nature of these bonds. Here, the authors report one-carbon insertion into aromatic C-N bonds to directly convert anilines to chiral benzylic amines.

Despite the fact that the introduction of a fluorine atom at the C-6 position has resulted in the evolution of fluoroquinolones, fluoroquinolone-induced cardiac toxicity has drawn considerable attention. In this context, desfluoroquinolone-based hybrids with involvement of C-7 aminopyrimidine functional group were designed and synthesized. The biological results showed majority of these hybrids still demonstrated potent anti-MRSA activity with MIC values between 0.38 and 1.5 μg/mL, despite the lack of the typical C-6 fluorine atom. Particularly, the most active B14 exhibited activities at submicromolar concentrations against a panel of MRSA strains including vancomycin-intermediate strains, levofloxacin-resistant isolates, and linezolid-resistant isolates, etc. As expected, it also displayed highly selective toxicity toward bacterial cells and low hERG inhibition. Further resistance development study indicated MRSA is unlikely to acquire resistance against B14. The docking study revealed that two hydrogen bonds were formed between the C-7 substituent and the surrounding DNA bases, which might contribute to overcome resistance by reducing the dependence on the magnesium-water bridge interactions with topoisomerase IV. These results indicate a promising strategy for developing new antibiotic quinolones to combat multidrug resistance and cardiotoxicity.

HIV-1 integrase (IN) is a key enzyme in viral replication that catalyzes the covalent integration of viral cDNA into the host genome. Currently, five HIV-1 IN strand transfer inhibitors (INSTIs) are approved for clinical use. These drugs represent an important addition to the armamentarium for antiretroviral therapy. This review briefly illustrates the development history of INSTIs. The characteristics of the currently approved INSTIs, as well as their future perspectives, are critically discussed.

An iodine(III)-induced regioselective intramolecular carbocyclization of functionally substituted terminal alkynes is reported. A range of 1,1-diiodomethylene substituted cyclic compounds were prepared by using iodide salts as the iodine source to replace the normally used electrophilic I2, NIS or ICl. The use of 2,2,2-trifluoroethanol as a solvent is essential for the generation of reactive iodine(III) species. The resulting diiodomethylene substituted cyclic compounds can be readily converted to tetra-substituted alkenes through transition metal-catalyzed coupling reactions.

Given the abundance and the ready availability of anilines, the selective insertion of atoms into the aryl carbon–nitrogen bonds will be an appealing route for the synthesis of nitrogen-containing aromatic molecules. However, because aryl carbon–nitrogen bonds are particularly inert, anilines are normally activated by conversion to more reactive intermediates such as aryldiazonium salts to achieve functionalization of the aryl carbon–nitrogen bonds, but the nitrogen atom is usually not incorporated into products, instead being discarded. The selective insertion of groups into aryl carbon–nitrogen bonds remains an elusive challenge and an unmet need in reaction design. Here we show an aromaticity destruction-reconstruction process that selectively inserts a trimethylenemethane (TMM) group into the aromatic carbon–nitrogen bond of anilines concomitant with a benzylic carbon–hydrogen bond functionalization. This process provides a transformative mode for anilines, and the insertion products are versatile precursor to various nitrogen-containing aromatic molecules through simple conversions., Activation of C–N bonds of anilines requires transformation of the amino group into a more reactive functionality. Here, the authors report an aromaticity destruction-reconstruction process that converts abundant anilines into valuable amines through group insertion into the C–N bond and benzylic C–H functionalization.

2-Alkynylanilines are attractive starting materials in indole synthesis because of their ready availability. Herein, a one-pot stepwise procedure is reported for efficient construction of multisubstituted oxocino[4,3,2-cd]indoles from 2-alkynylanilines and 2-alkynylbenzaldoximes. The method comprises the oxidative dearomatization of 2-alkynylanilines, the silver-catalyzed [3+3] cycloaddition with 2-alkynylbenzaldoximes, and subsequent thermal radical skeletal rearrangement and aromatization.

A PhIO/Bu4NI-mediated oxidative cross-coupling reaction between enamines and propargylamines under metal-free conditions has been developed. Bu4NI works as an activator of PhIO. The resulting coupling products are ready to undergo copper(II)-mediated electrophilic cyclization to form highly substituted 3-pyrrolines.

A novel PhI(OAc)2-mediated dialkoxylation of 4-aminostyrenes has been developed. A range of 2,3-disubstituted 1,4-dioxane or 1,2-dimethoxyethane derivatives were formed in 15 to 95% yields with high diastereoselectivities. This transformation was distinct from the previously reported hypervalent iodine(III)-mediated dioxygenation reaction, a process via the formation of a cyclic iodonium ion intermediate. This protocol involves an oxidative dearomatization-induced nucleophilic attack and an aromatization-induced 1,6-conjugated addition.

An oxidative nucleophilic cyclization of 2-alkynylanilines with thiophenols under metal-free conditions was developed. The one-pot two-step reaction involves a PhI(OAc)2-mediated oxidative dearomatization and a Brønsted acid promoted nucleophilic cyclization. DFT calculations were performed to understand the reaction pathway.

Synthetically useful 4-acetonylindoles have been conveniently prepared from 2-alkynylanilines and silyl enol ethers using a dearomatization strategy. The two-step/one-pot protocol involves an iodosylbenzene-mediated oxidative dearomatization and a silver-catalyzed domino reaction.

A facile approach to construct 3,4-fused tricyclic azepino[5,4,3-cd]indoles from 2-alkynyl anilines, isocyanides, and α,β-unsaturated acids is reported. This synthetic process involves a regioselective meta-functionalization of 2-alkynylanilines using a dearomatization strategy and a palladium(II)-catalyzed domino heterocyclization/Heck reaction.

A dearomatization strategy of β-enamino esters was developed to construct indenoazepine derivatives. The oxidative dearomatization was combined with a base-promoted tandem Michael addition/polycyclization and an acid-catalyzed aromatization. The nonaromatic structure of the Michael adducts might be essential to the realization of the 7-endo-dig cyclization.

Metal-controlled cycloaddition of 2-alkynyl-1,4-benzoquinones and electron-rich styrenyl systems were investigated. The density functional theory (DFT) calculations revealed that the regioselectivity of the cycloaddition results from the different activation modes of Bi(OTf)3 and AuCl.

A one-pot synthetic strategy for diarylamines using only aromatic amines as starting materials has been developed. This method involved a PhI(OAc)2-induced oxidative dearomatization of N-sulfonyl protected para-substituted anilines, a Bi(OTf)3-catalyzed imino exchange reaction between N-sulfonyl cyclohexadienimines and aromatic amines, and a CF3COOH/Zn mediated reductive aromatization of the resulting N-aryl cyclohexadienimines.

Dearomatization provides numerous possibilities for the development of new transformative modes of aromatic compounds. A conceptually novel metal-free multicomponent domino reaction of the dearomatized products of 2-alkynylanilines is developed. The reaction involves the secondary amine-mediated transimination with α-amino nitriles and subsequent aromatization-triggered cascade rearrangement, nucleophilic cyclization, and retro-Strecker reaction. This process provided a new practical method for the rapid synthesis of polyfunctionalized 4-aminoquinolines from readily available starting materials.

A dearomatization strategy has been developed for the efficient construction of vertically expanded five-ring fused benzofurans from ortho-alkynylphenols and ortho-alkynylarylaldimines. The stepwise procedure comprises a dearomatization-induced silver-catalyzed [3 + 2] cycloaddition followed by an aromatization-triggered ytterbium-catalyzed rearrangement.

The approach involves an oxidative dearomatization of 2-alkynylanilines, a silver-catalyzed [3+3] cycloaddition with 2-alkynylbenzaldoximes, and a subsequent thermal radical skeletal rearrangement and aromatization.

Oxidative dearomatization of N-tosylated anilines and subsequent reaction with cyanoacetates and related cyano substituted activated methylene compounds followed by the addition of an external nucleophile offers a straightforward access to arenes substituted with a quarternary carbon.

As a powerful tool, the dearomatization of phenols has been explored extensively and utilized by organic chemists during the course of complex syntheses. This review highlights recent advances in phenol dearomatizations, especially those accomplished in an enantioselective manner, and the application of dearomatization strategies in complex syntheses. 1 Introduction 2 New Developments in Phenol Dearomatization 3 Enantioselective Phenol Dearomatization 3.1 Controlled by Chiral Substrate 3.2 Controlled by Chiral Catalyst 3.3 Controlled by Chiral Hypervalent Iodine 4 Enantioselective Phenol Dearomatization Strategies in Complex Syntheses 4.1 With the Formation of a Carbon–Oxygen Bond 4.2 With the Formation of a Carbon–Carbon Bond 4.3 With the Formation of a Carbon–Nitrogen Bond 5 Conclusion

Six genes, which encode enzymes involved in ascorbic acid (AsA) biosynthesis, including guanosine diphosphate (GDP)-mannose pyrophosphorylase (GMP), GDP-mannose-3′,5′-epimerase (GME), GDP-galactose guanylyltransferase (GGT), L-galactose-1-phosphate phosphatase (GPP), L-galactose dehydrogenase (GDH) and L-galactono-1,4-lactone dehydrogenase (GLDH) were transformed into Arabidopsis thaliana, to evaluate the contribution of each gene to AsA accumulation. Additionally, two combinations, GGT-GPP and GGT-GLDH, were co-transformed into Arabidopsis with a reliable double-gene transformation system. AsA content of GGT transgenic lines was 2.9-fold higher as compared to the control, and co-transformation led up to 4.1-fold AsA enhancement. These results provided further evidence that GGT is the key enzyme in plant AsA biosynthesis.

Radiotherapy is the major treatment for nasopharyngeal carcinoma, a malignant tumor of epithelial origin. In this process, a tracer with high sensitivity is pivotal for diagnostic imaging in radiotherapy. Here, we designed a novel multifunctional magnetic silver nanocomposite, Fe(3)O(4)/Ag conjugated to an epidermal growth factor receptor-specific antibody (C225), which can be potentially used for synchronous cancer therapy and diagnosis via magnetic resonance imaging. Characteristics of Fe(3)O(4)/Ag/C225 were determined by transmission electron microscopy, energy dispersive X-ray spectroscopy, ultraviolet spectra, and dynamic light scattering. The results demonstrated that Fe(3)O(4)/Ag/C225 nanoparticles were spherical and dispersed well in water. The activity of C225 was preserved ∼80% in the Fe(3)O(4)/Ag/C225 nanoparticles. Futhermore, we tested the cytotoxicity and radiosensitivity of the nanocomposite for human nasopharyngeal carcinoma cell lines (CNEs) in vitro. MTT analysis revealed that Fe(3)O(4)/Ag/C225 could inhibit the proliferation of CNEs in a dose- and time-dependent manner. The clonogenic assay indicated that Fe(3)O(4)/Ag/C225 combined with X-ray treatment could increase the sensitivity of CNEs to irradiation. In a summary, the novel multifunctional nanocomposite Fe(3)O(4)/Ag/C225 might be a potential radiosensitizer for treating malign tumors in the clinic.

The oxidative dearomatization of para-substituted o-alkynylanilines afforded 2-alkynyl cyclohexadienimines, which can act as active substrates for reaction with electron-rich styrenes. The reaction is metal-controlled. Bi(OTf)3-catalyzed reactions afforded 3,4-dihydro-cyclopenta[c,d]indoles, and AgOTf-catalyzed reactions provided tricyclic pyrrole derivatives.

An efficient method to construct oxa-aza spirobicycles via an iodine(III)-mediated tandem carbon-hydrogen bond oxidation with the combination of iodobenzene diacetate and tetrabutylammonium iodide is reported.

Organic nanotubes have been assembled from pillar[5]arenes 1 and 2. Compound 1 gelates organic solvents through the formation of tubular fibers which are evidenced by TEM and XRD experiments, while 2 assembles into two different channels under the template effect of water wires. In addition, the water wires in the nanotubes of 2 can be under selective proton conductance. The results described herein represent a new strategy for building tubular structures.

Hypoxia is a common environmental stress factor and is associated with fibrogenesis. Matrix metalloproteinase-2 (MMP-2), produced by hepatic stellate cells (HSCs), plays an important role in liver fibrogenesis. However, inconsistent results have been reported on the impact of hypoxia on MMP-2 expression and activity in HSCs. We speculated that cell–cell interaction is involved in the regulation of MMP-2 expression and activity at low oxygen level in vivo. Therefore, in this report we investigated the mechanism by which hypoxic hepatocytes regulates MMP-2 expression in HSCs. Our results showed that the conditioned medium from hypoxia-treated rat hepatocytes strongly induced the expression of MMP-2 mRNA and protein in rat HSC-T6 cells. Reduced glutathione neutralized ROS released from hypoxic hepatocytes, leading to reduced MMP-2 expression in HSC-T6 cells. In addition, phospho-IκB-α protein level was increased in HSC-T6 cells treated with hypoxia conditioned medium, and NF-κB signaling inhibitor inhibited MMP-2 expression in HSC-T6 cells. Taken together, our data suggest that ROS is an important factor released by hypoxic hepatocytes to regulate MMP-2 expression in HSCs, and NF-κB signaling is crucially involved in ROS-induced MMP-2 expression in HSCs. Our findings suggest that strategies aimed at antagonizing the generation of ROS in hypoxic hepatocytes and inhibiting NF-κB signaling in HSCs may represent novel therapeutic options for liver fibrosis.

An oxidative coupling strategy involving hypervalent organoiodine-inducedoxidative dearomatization of 4-substituted phenols, Bronstedacid catalyzed Michael addition with indoles, and aromatizationhas been developed. The one-pot reaction provides an efficient accessto the META-indole-substituted phenolderivatives.

A selective C3—C3 oxidative cross-cou- I pling between unactivated anilines and indoles catalyzed by copper bromide together with iodobenzene diacetate as the oxidant is described. This methodology provides a novel approach to biaryl synthesis.

In this paper, we report a facile synthesis of 2-carbamoyl-2-cyanocyclopropanecarboxylates through a tandem iodosobenzene/tetrabutylammonium iodide-induced oxidative cyclization and a subsequent neighboring group-assisted decarboxylation of the Michael adducts of 2-cyanoacetamides with α,β-unsaturated malonates. This method affords the desired highly functionalized cyclopropanes in moderate to good yields and with excellent diastereoselectivities. In addition, the reaction proceeds smoothly under mild conditions and with good functional group tolerance.