Construction of Bridged Benzazepines via Photo-Induced Dearomatization.

Bridged benzazepine scaffolds, possessing unique structural and physicochemical activities, are widespread in various natural products and drugs. The construction of these skeletons often requires elaborate synthetic effort with low efficiency. Herein, we develop a simple and divergent approach for constructing various bridged benzazepines by a photocatalytic intermolecular dearomatization of naphthalene derivatives with readily available α-amino acids. The bridged motif is created via a cascade sequence involving photocatalytic 1,4-hydroaminoalkylation, alkene isomerization and cyclization. Interestingly, the diastereoselectivity can be regulated through different reaction modes in the cyclization step. Moreover, aminohydroxylation and its further bromination have also been demonstrated to access highly functionalized bridged benzazepines. Preliminary mechanistic studies have been performed to get insights into the mechanism. This method provides a divergent synthetic approach for construction of highly functionalized bridged benzazepines, which have been otherwise difficult to access.

Hydrated [3+2] Cyclotelomerization of Butafulvenes to Create Multiple Contiguous Fully Substituted Carbon Centers.

The construction of multiple continuous fully substituted carbon centers, which serve as unique structural motif in natural products, is a challenging topic in organic synthesis. Herein, we report a hydrated [3+2] cyclotelomerization of butafulvenes to create contiguous fully substituted carbon backbone. In the presence of scandium triflate, all-carbon skeleton with spiro fused tricyclic ring can be constructed in high diastereoselectivity by utilizing butafulvene as the synthon. Mechanistic studies suggest that this atom-economic reaction probably proceeds through a synergistic process containing butafulvenes dimerization and nucleophilic attack by water. In addition, the tricyclic product can undergo a series of synthetic derivatizations, which highlights the potential applications of this strategy. The recyclability of Sc(OTf)3 has also been demonstrated to show its robust performance in this hydrated cyclotelomerization.

Rhodium-Catalyzed Deuterated Tsuji-Wilkinson Decarbonylation of Aldehydes with Deuterium Oxide.

The recent surge in the applications of deuterated drug candidates has rendered an urgent need for diverse deuterium labeling techniques. Herein, an efficient Rh-catalyzed deuterated Tsuji-Wilkinson decarbonylation of naturally available aldehydes with D2O is developed. In this reaction, D2O not only acts as a deuterated reagent and solvent but also promotes Rh-catalyzed decarbonylation. In addition, decarbonylative strategies for the synthesis of terminal monodeuterated alkenes from α,ß-unsaturated aldehydes are within reach.

Reactivity of ynamides in catalytic intermolecular annulations.

Ynamides are unique alkynes with a carbon-carbon triple bond directly attached to the nitrogen atom bearing an electron-withdrawing group. The alkyne is strongly polarized by the electron-donating nitrogen atom, but its high reactivity can be finely tempered by the electron-withdrawing group. Accordingly, ynamides are endowed with both nucleophilic and electrophilic properties and their chemistry has been an active research field. The catalytic intermolecular annulations of ynamides, featuring divergent assembly of structurally important amino-heterocycles in a regioselective manner, have gained much attention over the past decade. This review aims to provide a comprehensive summary of the advances achieved in this area involving transition metal and acid catalysis. Moreover, the intermolecular annulations of ynamide analogs including ynol ethers and thioalkynes are also discussed, which can provide insights into the reactivity difference caused by the heteroatoms.

MiR-410-3p activates the NF-κB pathway by targeting ZCCHC10 to promote migration, invasion and EMT of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract. miR-410-3p is involved in oncogenesis and development of CRC, but the specific regulation mechanism is still not known clearly. METHODS: The expression of miR-410-3p and zinc finger CCHC-type containing 10 (ZCCHC10) in CRC cells was detected by qRT-PCR and western blot method, respectively. The dual-luciferase reporter gene detection was applied for determination of interaction between miR-410-3p and ZCCHC10. The wound healing assay and transwell assay were carried out to measure cell migration and invasive ability, respectively. RESULTS: The miR-410-3p expression levels were markedly increased, but ZCCHC10 levels were reduced in CRC cells and tissues. Dual-luciferase reporter gene detection indicated that miR-410-3p targeted ZCCHC10 directly. Functionally knockdown of ZCCHC10 or overexpression of miR-410-3p activated nuclear factor-κB (NF-κB) signaling pathway, promoted epithelial-mesenchymal transition (EMT) process, as well as cell migration and invasion of CRC cells. After adding NF-κB inhibitor BAY 11-708 to inhibit NF-κB pathway, the promoting effects of si-ZCCHC10 on cell migration, invasion and EMT of HT29 and SW480 cells were suppressed. Meanwhile, overexpression of ZCCHC10 inhibited the effects of miR-410-3p on cell migration, invasion and EMT of HT29 and SW480. CONCLUSION: miR-410-3p-mediated ZCCHC10 suppression regulates NF-κB activation, thereby promoting EMT process, cell migration and invasion of CRC cells. This study provides a new insight into the specific mechanism by which miR-410-3p mediates CRC progression.

Visible Light Induced Bifunctional Rhodium Catalysis for Decarbonylative Coupling of Imides with Alkynes.

Transition metal catalyzed decarbonylation offers a distinct synthetic strategy for new chemical bond formation. However, the π-backbonding between CO π* orbitals and metal center d-orbitals impedes ligand dissociation to regenerate the catalyst under mild reaction conditions. Developed here is visible light induced rhodium catalysis for decarbonylative coupling of imides with alkynes under ambient conditions. Initial mechanistic studies suggest that the rhodium complex simultaneously serves as the catalytic center and photosensitizer for decarbonylation. This visible light promoted catalytic decarbonylation strategy offers new opportunities for reviewing old transformations with ligand dissociation as a rate-determining step.

Copper-catalyzed boroacylation of allenes to access tetrasubstituted vinylboronates.

A distinct copper-catalyzed boroacylation of allenes with acyl chlorides and bis(pinacolato)diboron is developed. For aromatic acyl chlorides, 1,2-boroacylation of allenes readily takes place, leading to the formation of tetrasubstituted vinylboronates with exclusive (E)-stereoselectivity. In comparison, the employment of alkyl acyl chlorides as electrophiles alters the selectivity to 2,3-boroacylated products. Additionally, the product can easily undergo Suzuki-Miyaura cross-coupling to afford tetrasubstituted alkene with complete retention of the configuration.

TET1 suppresses colon cancer proliferation by impairing ß-catenin signal pathway.

The function of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in cancer is background dependent and may be involved in the initial step of active DNA demethylation, while there is little research to decipher the role of TET1 in DNA methylation-sensitive colon cancer. Downregulated TET1 expression assayed by quantitative real-time PCR (qRT-PCR) was observed in both colon cancer samples and cancer cell lines of HT29, HCT116, and SW48. Such downregulation could promote colon cancer cells proliferation as indicated by the fact that shTET1 could increase the viability of HT29 and HCT116 cells determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and cell count assay accompanied with upregulation of ß-catenin (CTNNB1) and WNT luciferase activity, which was further confirmed as shTET1 could increase the tumor volume and tumor weight, and decrease the body weight in HT29 cells inoculated BALB/C nude mice. The CTNNB1 transfection could rescue the cell growth diminished by normal expression of TET1. shTET1 could promote axis inhibition protein1 (AXIN1) expression and the cell proliferation effect induced by TET1 short hairpin RNA was attenuated by co-inhibition of AXIN1. All of these indicate that TET1 can suppress colon cancer proliferation and the inhibition of the ß-catenin pathway is AXIN1 dependent.

Treatment of colon cancer in a patient with systemic lupus erythematosus: a case report.

BACKGROUND: Gastrointestinal symptoms occur in approximately 50% of patients with systemic lupus erythematous with low specificity. Although it is well established that colon cancer is one of the many gastrointestinal manifestations associated with systemic lupus erythematous, the diagnosis and treatment remains complex due to adrenal insufficiency symptoms. CASE PRESENTATION: A 43-year-old Chinese woman with a five-year history of systemic lupus erythematous was diagnosed with colon cancer based on imaging test. A radical bowel resection was performed successfully. To avoid serious complications during surgery, prednisone was replaced with methylprednisolone therefore avoiding adrenal insufficiency. The patient was subsequently treated with mFOLFOX6 chemotherapy and recovered well. CONCLUSION: There is a lack of reports for treatment of colon cancer in patients with systemic lupus erythematous. This report provides an effective way to diagnose colon cancer in patients with systemic lupus erythematous and illustrates a successful therapy strategy for this complex medical condition.

Enantiodivergent Desymmetrization in the Rhodium(III)-Catalyzed Annulation of Sulfoximines with Diazo Compounds.

RhIII - and IrIII -catalyzed asymmetric C-H functionalization reactions of arenes have relied on the employment of chiral RhIII /IrIII cyclopentadienyl catalysts, the introduction of chiral carboxylic acids to achiral Cp*RhX2 catalysts, and the integration of both strategies. Despite considerable progress, each reaction only provided a specific configuration of the enantioenriched product when using a particular chiral catalyst. Reported in this work is the enantiodivergent coupling of sulfoximines with various diazo compounds by RhIII -catalyzed desymmetrizing annulation. The enantiodivergence was enabled by a judicious choice of achiral carboxylic acids, and the enantioselectivity correlates with the steric bias of the carboxylic acid and the sulfoximine.

Photocatalytic H2 production using a hybrid assembly of an [FeFe]-hydrogenase model and CdSe quantum dot linked through a thiolato-functionalized cyclodextrin.

It is a great challenge to develop iron-based highly-efficient and durable catalytic systems for the hydrogen evolution reaction (HER) by understanding and learning from [FeFe]-hydrogenases. Here we report photocatalytic H2 production by a hybrid assembly of a sulfonate-functionalized [FeFe]-hydrogenase mimic (1) and CdSe quantum dot (QD), which is denoted as 1/ß-CD-6-S-CdSe (ß-CD-6-SH = 6-mercapto-ß-cyclodextrin). In this assembly, thiolato-functionalized ß-CD acts not only as a stabilizing reagent of CdSe QDs but also as a host compound for the diiron catalyst, so as to confine CdSe QDs to the space near the site of diiron catalyst. In addition, another two reference systems comprising MAA-CdSe QDs (HMAA = mercaptoacetic acid) and 1 in the presence and absence of ß-CD, denoted as 1/ß-CD/MAA-CdSe and 1/MAA-CdSe, were studied for photocatalytic H2 evolution. The influences of ß-CD and the stabilizing reagent ß-CD-6-S- on the stability of diiron catalyst, the fluorescence lifetime of CdSe QDs, the apparent electron transfer rate, and the photocatalytic H2-evolving efficiency were explored by comparative studies of the three hybrid systems. The 1/ß-CD-6-S-CdSe system displayed a faster apparent rate for electron transfer from CdSe QDs to the diiron catalyst compared to that observed for MAA-CdSe-based systems. The total TON for visible-light driven H2 evolution by the 1/ß-CD-6-S-CdSe QDs in water at pH 4.5 is about 2370, corresponding to a TOF of 150 h-1 in the initial 10 h of illumination, which is 2.7- and 6.6-fold more than the amount of H2 produced from the reference systems 1/ß-CD/MAA-CdSe and 1/MAA-CdSe. Additionally, 1/ß-CD-6-S-CdSe gave 2.4-5.1 fold enhancement in the apparent quantum yield and significantly improved the stability of the system for photocatalytic H2 evolution.

Tf2NH-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with Dioxazoles: A Metal-Free Approach to Polysubstituted 4-Aminooxazoles.

An unprecedented Tf2NH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.

Tf2NH-catalyzed formal [3 + 2] cycloaddition of oxadiazolones with ynamides: a simple access to aminoimidazoles.

Oxadiazolones are first employed as the three-atom coupling partners in the Tf2NH-catalyzed cycloaddition with ynamides. This formal [3 + 2] cycloaddition allows a rapid synthesis of aminoimidazoles with a broad substrate scope. The approach also features a metal-free catalytic cycloaddition process, which may find applications in the synthesis of bioactive molecules. Besides, the resulting N-methyl products can further be readily converted to free N-H aminoimidazoles.

Transition-Metal Controlled Diastereodivergent Radical Cyclization/Azidation Cascade of 1,7-Enynes.

A strategy for achieving diastereodivergent azidations of enynes has been developed, employing azide transfer from the M-N3 complex to alkyl radicals. Following this concept, the diastereoselectivity has been switched by modulating the transition metals and the ligands. The Mn(III)-mediated radical cyclization/azidation cascade of 1,7-enynes afforded trans-fused pyrrolo[3,4-c]quinolinones, whereas the Cu(II)/bipyridine system gave cis-products.

Ruthenium-Catalyzed [3 + 2] Cycloaddition of 2H-Azirines with Alkynes: Access to Polysubstituted Pyrroles.

A ruthenium-catalyzed intermolecular [3 + 2] cycloaddition of 2H-azirines and activated alkynes is reported, which provides polysubstituted pyrroles in moderate to good yields. This approach features a C-N bond cleavage of 2H-azirines by a ruthenium catalyst. The results of this study would provide a complementary method to synthesize polysubstituted pyrroles from the known 2H-azirine approaches and advance 2H-azirine chemistry.

Selective synthesis of functionalized pyrroles from 3-aza-1,5-enynes.

2-Trifluoromethyl-5-(arylsulfonyl)methyl pyrroles and 2-trifluoromethyl-4-(arylsulfonyl)methyl pyrroles were selectively synthesized from trifluoromethyl-substituted 3-aza-1,5-enynes via a cyclization/sulfonyl group migration cascade catalyzed by AgOOCCF3 and CsOPiv, respectively. Alkylvinyl-substituted pyrroles were generated from seven-atom skeleton 3-aza-1,5-enynes via aryl sulfinic acid elimination in the presence of Cs2CO3. Two ion-pair intermediates were proposed and a key intermediate, aza-diene-yne, was successfully isolated in the mechanistic studies.

Ruthenium-Catalyzed C-C Bond Cleavage of 2H-Azirines: A Formal [3+2+2] Cycloaddition to Fused Azepine Skeletons.

2H-azirines can serve as three-atom synthons by C-C bond cleavage, however, it involves a high energy barrier under thermal conditions (>50.0 kcal mol(-1) ). Reported is a ruthenium-catalyzed [3+2+2] cycloaddition reaction of 2H-azirines with diynes, thus leading to the formation of fused azepine skeletons. This approach features an unprecedented metal-catalyzed C-C bond cleavage of 2H-azirines at room temperature, and the challenging construction of aza-seven-membered rings from diynes. The results of this study provide a new reaction pattern for constructing nitrogen-containing seven-membered rings and may find applications in the synthesis of other complex heterocycles.

Rhodium-catalyzed C-H activation of phenacyl ammonium salts assisted by an oxidizing C-N bond: a combination of experimental and theoretical studies.

Rh(III)-catalyzed C-H activation assisted by an oxidizing directing group has evolved to a mild and redox-economic strategy for the construction of heterocycles. Despite the success, these coupling systems are currently limited to cleavage of an oxidizing N-O or N-N bond. Cleavage of an oxidizing C-N bond, which allows for complementary carbocycle synthesis, is unprecedented. In this article, α-ammonium acetophenones with an oxidizing C-N bond have been designed as substrates for Rh(III)-catalyzed C-H activation under redox-neutral conditions. The coupling with α-diazo esters afforded benzocyclopentanones, and the coupling with unactivated alkenes such as styrenes and aliphatic olefins gave ortho-olefinated acetophenoes. In both systems the reactions proceeded with a broad scope, high efficiency, and functional group tolerance. Moreover, efficient one-pot coupling of diazo esters has been realized starting from α-bromoacetophenones and triethylamine. The reaction mechanism for the coupling with diazo esters has been studied by a combination of experimental and theoretical methods. In particular, three distinct mechanistic pathways have been scrutinized by DFT studies, which revealed that the C-H activation occurs via a C-bound enolate-assisted concerted metalation-deprotonation mechanism and is rate-limiting. In subsequent C-C formation steps, the lowest energy pathway involves two rhodium carbene species as key intermediates.

Silica modified with a thiourea derivative as a new stationary phase for hydrophilic interaction liquid chromatography.

Nowadays there are limited types of commercially available stationary phases for hydrophilic interaction liquid chromatography and therefore new ones with unique selectivity are urgently in demand to meet the need of separations of various polar and hydrophilic analytes. The present study describes the preparation and evaluation of a new stationary phase based on thiourea derivative modified silica for hydrophilic interaction liquid chromatography. Thiourea derivative was bonded onto the surface of silica particles via a mild addition reaction between -NH2 and -SCN, and the result of elemental analysis together with infrared analysis and solid-state NMR spectroscopy proved that the synthesis method was feasible. The new stationary phase succeeded in fast separations of a wide range of polar and hydrophilic analytes and exhibited excellent separation performance, especially unique selectivity. Furthermore, the effects of water content, buffer pH, and salt concentration on retention indicated that a complicated separation mechanism rather than partitioning was involved in the stationary phase and hydrogen bonding interaction between analytes and thiourea functional group could play a very important role in its selectivity. For sure, the new stationary phase is of a great potential as a new type of hydrophilic interaction liquid chromatographic stationary phase.

Rhodium-Catalyzed C-H Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3-Diaryl-Substituted Indoles.

The direct C-H annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3-disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3-diaryl substituted indoles. Herein, we report the rhodium(III)-catalyzed C-H annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3-diaryl-substituted N-unprotected indoles with two different aryl groups. One of the aryl substituents is derived from N=C-aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.