Photoinduced Borylation of the Inert C(sp3)-O Bond of Alkyl Heteroaryl Ethers.

A photoinduced reductive Calkyl-O borylation of alkyl heteroaryl ethers with very negative reduction potential in the presence of 4-dimethylaminopyridine (DMAP) and bis(catecholato)diborane(B2cat2) was developed. Despite the high reducing power, various substrates with liable functional groups were well-tolerated as well as ethers derived from natural products and medicinal-relevant compounds. Mechanistic investigation implied that an intra-single electron transfer process in an electron donor-acceptor complex formed from ethers with the adduct of B2cat2 and DMAP should be involved.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS: The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids via Hydrogen Atom Transfer.

The oxidation of primary alcohols and aldehydes to the corresponding carboxylic acids is a fundamental reaction in organic synthesis. In this paper, we report a new chemoselective process for the oxidation of primary alcohols and aldehydes. This metal-free reaction features a new oxidant, an easy to handle procedure, high isolated yields, and good to excellent functional group tolerance even in the presence of vulnerable secondary alcohols and tert-butanesulfinamides.

Synthesis of Highly Functionalized Pyridines: A Metal-Free Cascade Process.

Herein, we report a new process for the synthesis of highly functionalized pyridines based on a tandem Pummerer-type rearrangement, aza-Prins cyclization, and elimination-induced aromatization. This formal [5+1] cyclization provides pyridines in good yields with easily accessible starting materials. The synthetic potential of our new method is further demonstrated in the modification of the frameworks of BINOL and some natural products.

Lewis acid mediated cyclization: synthesis of 2 spirocyclohexylindolines.

Herein, we report the synthesis of 2-spirocyclohexylindolines based on a Lewis acid mediated cyclization. This diastereoselective procedure provides the target structures in a straightforward way via dual activation.

Iron-Catalyzed Decarboxylative Olefination of Cycloketone Oxime Esters with α,ß-Unsaturated Carboxylic Acids via C-C Bond Cleavage.

An iron-catalyzed redox-neutral, decarboxylative olefination of cycloketone oxime esters with α,ß-unsaturated carboxylic acids has been developed. This reaction involves an iminyl radical mediated C-C bond cleavage/radical addition/decarboxylation cascade. This protocol is highlighted by its low-cost catalytic system and readily accessible starting materials, as well as broad substrate scope, thus providing facile access to structurally diverse cyano-containing alkenes.

Synthesis and anti-proliferative activity of allogibberic acid derivatives containing 1,2,3-triazole pharmacophore.

Sixty novel allogibberic acid derivatives containing 1,2,3-triazole pharmacophore were designed and synthesized. The key chemical processes include aromatization of the A ring in gibberellins, formation of allogibberic azides and its copper mediated Huisgen 1,3-dipolar cycloaddition with alkynes. A number of hybrids containing α,ß-unsaturated ketone moiety exhibited excellent in vitro cytotoxic activities. Some of the hybrids were more selective to MCF-7 and SW480 cell lines with IC50 values at least 8-fold more cytotoxic than cisplatin (DDP). The most potent compounds C43 and C45 are more cytotoxic than cisplatin (DDP) against all tested five tumor cell lines, with IC50 values of 0.25-1.72 µM. Mechanism of action studies indicated that allogibberic-triazole derivative C45 could induce the S phase cell cycle arrest and apoptosis in SMMC-7721 cell lines.

Identification of novel dual-specificity phosphatase 26 inhibitors by a hybrid virtual screening approach based on pharmacophore and molecular docking.

Dual-specificity phosphatase 26 (DUSP26) has recently emerged as a target for treatment of human cancers. However, only two small-molecule inhibitors of DUSP26 are known so far, namely NSC-87877 and ethyl-3, 4-dephostatin. DUSP26 contains an N-terminal region (residues 1-60) and a conserved C-terminal catalytic domain (residues 61-211, DUSP26-C). The crystal structure of DUSP26-C, showing a catalytically inactive conformation of the active site, was reported in a previous study. However, the detailed catalytic mechanism of DUSP26 cannot be described based on that structure. In this study, the 3D structure of DUSP26 (residues 42-211) adopting catalytically active conformation, was built by homology modeling, and the established 3D structure was validated using enzyme kinetic assays. Pharmacophore modeling based on the validated 3D structure of human DUSP26 was carried out. The established pharmacophore model was considered as a 3D query for retrieving novel DUSP26 inhibitors from the chemical databases "Diversity Libraries" (129,087 compounds). Next, a docking study was performed to refine the obtained hit compounds. Then a total of 100 compounds were selected based on the ranking order and visual examination, which were then evaluated by an enzyme-based assay. Eight compounds were found to have inhibitory activities against DUSP26, and the most potent compound was assigned No. F1063-0967 with an IC50 value of 11.62µM. The inhibitory activity of F1063-0967 against DUSP26 is higher than that of NCS87877 (IC50 value: 16.67±2.89µM), but lower than that of ethyl-3, 4-dephostatin (IC50 value: 6.8±0.41µM). MTT assay results revealed that F1063-0967 can induce apoptosis in IMR-32 cell line with an IC50 value of 4.13µM. These results suggest that F1063-0967 should be investigated further for other pharmacological properties.

Transition-Metal-Free Oxyfluorination of Olefinic Amides for the Synthesis of Fluorinated Heterocycles.

A series of fluorinated 4H-3,1-benzoxazines and iminoisobenzofurans have been synthesized through the electrophilic fluorocyclization of olefinic amides. This methodology is highlighted by its mild conditions, wide substrate scope, and good functional group tolerance.

Transition-metal-free tandem radical thiocyanooxygenation of olefinic amides: a new route to SCN-containing heterocycles.

A novel transition-metal-free tandem radical thiocyanooxygenation of olefinic amides with potassium thiocyanate has been developed under mild conditions. This method allows a reliable and practical access to diverse SCN-containing heterocycles bearing a wide range of functional groups in good to excellent yields. Furthermore, this tandem reaction provides a simple method for the construction of C-O and C-S bonds in one step.

Design, synthesis and aromatase inhibitory activities of novel indole-imidazole derivatives.

A series of novel indole-imidazole derivatives have been prepared and evaluated in vitro on the aromatase inhibitory activities. The results suggested that proton or a small electron-withdrawing group at para-position of the phenyl ring would enhance the inhibitory activities and any bulky group should be avoided in order to keep a relative small volume for this kind of molecules.

Molecular mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and atherosclerosis.

SCOPE: Curcumin, a potent antioxidant extracted from Curcuma longa, confers protection against atherosclerosis, yet the detailed mechanisms are not fully understood. In this study, we examined the effect of curcumin on lipid accumulation and the underlying molecular mechanisms in macrophages and apolipoprotein E-deficient (apoE⁻/⁻) mice. METHODS AND RESULTS: Treatment with curcumin markedly ameliorated oxidized low-density lipoprotein (oxLDL)-induced cholesterol accumulation in macrophages, which was due to decreased oxLDL uptake and increased cholesterol efflux. In addition, curcumin decreased the protein expression of scavenger receptor class A (SR-A) but increased that of ATP-binding cassette transporter (ABC) A1 and had no effect on the protein expression of CD36, class B receptor type I (SR-BI), or ATP-binding cassette transporter G1 (ABCG1). The downregulation of SR-A by curcumin was via ubiquitin-proteasome-calpain-mediated proteolysis. Furthermore, the curcumin-induced upregulation of ABCA1 was mainly through calmodulin-liver X receptor α (LXRα)-dependent transcriptional regulation. Curcumin administration modulated the expression of SR-A, ABCA1, ABCG1, and SR-BI in aortas and retarded atherosclerosis in apoE⁻/⁻ mice. CONCLUSION: Our findings suggest that inhibition of SR-A-mediated oxLDL uptake and promotion of ABCA1-dependent cholesterol efflux are two crucial events in suppression of cholesterol accumulation by curcumin in the transformation of macrophage foam cells.

2-[(1H-Imidazol-1-yl)meth-yl]-1-[4-(trifluoro-meth-yl)phen-yl]-1H-indole.

In the title compound, C(19)H(14)F(3)N(3), the dihedral angles between the mean planes of the indole ring and the 4-CF(3)-phenyl and imidazole rings are 54.95 (4) and 61.36 (7)°, respectively.

Novel cytotoxic chalcones from Litsea rubescens and Litsea pedunculata.

Two novel flavonoids with chalcone skeleton, together with seven known flavonoids, were isolated from the stem barks of Litsea rubescens and Litsea pedunculata. The structures of the new compounds were elucidated on the basis of spectral methods including IR, UV, 1D and 2D NMR. The new chalcones were found to contain the rare epoxy or ethylidenedioxy group. This is the first report on the presence of chalcone in the plant genus Litsea. The cytotoxic potential of two new chalcones was evaluated in vitro against three human tumor cell lines. Both new chalcones displayed potent cytotoxic activities against myeloid leukaemia (HL-60) and epidermoid carcinoma (A431) cell lines and more active than cisplatin (DDP). Interestingly, compound 1 exhibited cytotoxic activity against HL-60 with IC(50) value 2.1-fold more sensitive to DDP.

A novel aryltetralone lignan from Litsea pedunculata.

A novel aryltetralone lignan, pedunculine A (1), together with a known lignan cagayanone A (2), was isolated from the leaves and twigs of Litsea pedunculata. The structure of the new lignan was elucidated on the basis of spectroscopic methods and single-crystal X-ray diffraction.

A novel norditerpenoid alkaloid from Aconitum macrorhynchum.

A novel norditerpenoid alkaloid, macrorhynine C (1), together with three known compounds, was isolated from Aconitum macrorhynchum. The structure of the new alkaloid was elucidated on the basis of spectral analyses as (1alpha,6alpha,16beta)-3-hydroxy-8-acetyloxy-13-hydroxy-1,6,16-trimethoxy-4-(methoxymethyl)-19-ene-aconitan-14-yl 4-methoxybenzoate (1). The novel compound was found to contain the rare C(19) = N azomethine group. Compounds 2-4 were obtained from this species for the first time.

[Studies on the chemical constituents of Litsea lancifolia].

OBJECTIVE: To study the chemical constituents of Litsea lancifolia. METHODS: AU compounds were isolated from the diethyl ether extract of the title herb by sillica gel column chromatogrphy, and their structures were identified by physical and chemical evidences and spectral methods. RESULTS: Seven compounds were isolated and identified as (-)-aristortetralone (1), dehydrodiisoeugenol ( 2), dihydrodehydrodiconifery alcohol ( 3) , 5,7-dimethoxy-3', 4'-methylenedioxyflavan-3-ol (4), p-hydroxy-benzoic acid (5), vanillin(6), p-sitosterol (7), respectively. CONCLUSION: All compounds are isolated from this plant for the first time.

Arylglycerol glucosides from Dracocephalum forrestii.

Three new arylglycerol glucosides, threo-guaiacylglycerol 3-O-(6-O-p-hydroxybenzoyl)-beta-D-glucopyranoside (1), threo-guaiacylglycerol 3-O-[6-O-(E)-p-coumaroyl]-beta-D-glucopyranoside (2) and threo-guaiacylglycerol 3-O-[6-O-(Z)-p-coumaroyl]-beta-D-glucopyranoside (3), together with seven known compounds were isolated from the whole plants of Dracocephalum forrestii and their structures were determined on the basis of spectroscopic evidences.

[Study on flavanols from Glochidion hirsutum].

OBJECTIVE: To investigate the flavanols from Glochidion hirsutum. METHOD: The column chromatographic methods were employed for the isolation and purification of the chemical constituents. The structures were elucidated by spectroscopic methods. RESULT: Five flavanols were isolated and identified as 3-O-(3-methylgalloyl) catechin (1), 3-O-( 3-methylgalloyl) gallocatechin (2), 3-O-galloylgallocatechin (3), gallocatechin (4), catechin (5). CONCLUSION: Compound 1 is a new compound. The other four compounds were isolated from this plant for the first time.

[The chemical constituents of Breynia rostrata].

AIM: To study the chemical constituents of Breynia rostrata Merr. METHODS: Chromatography was used to isolate and purify the chemical constituents, their structures were identified by spectral analysis. RESULTS: Four glycosides were identified as 6-O-methylpropanoyl-alpha-D-glucopyranoside (1), 4"-phenolic-6-O-methylpropanoyl-beta-D-glucopyranoside (2), 1-O-galloyl-beta-D-glucopyranoside (3), arbutin (4). CONCLUSION: Compounds 1 and 2 are new compounds; 3 and 4 were isolated from Breynia rostrata Merr. for the first time.