Synthesis of 5,6-Dihydrophenanthridines via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C-H Bonds.

5,6-Dihydrophenanthridines are common aza heterocycle frameworks of natural products and pharmaceuticals. Herein, we reported the first palladium-catalyzed intramolecular C-H/C-H dehydrogenative coupling reaction of two simple arenes to generate 5,6-dihydrophenanthridines. The approach features a broad substrate scope and good tolerance of functional groups, offering an efficient alternative synthesis route for important 5,6-dihydrophenanthridine compounds.

Synthesis of Aporphine Analogues via Palladium-Catalyzed Intramolecular Aryl-Aryl Dehydrogenative Coupling.

Reported herein is an intramolecular dehydrogenative coupling of two inert aryl C-H bonds for the synthesis of aporphine analogues. The process represents a novel tool for the preparation of aporphines via palladiun-catalyzed C-H bond activation. The present reaction is compatible with various functional groups, and the coupling products have been further applied for the synthesis of natural products aporphine and zenkerine.

Photocatalyzed Csp3-Csp3 cross-dehydrogenative coupling of N-Boc-tetrahydroisoquinolines with α,ß-unsaturated ketones.

A novel photocatalyzed cross-dehydrogenative coupling reaction of N-Boc-tetrahydroisoquinolines with α,ß-unsaturated ketones has been developed. This research provides an easy access to a variety of C1-substituted tetrahydroisoquinolines, which can be further transformed into benzo[a]-quinolizine-2-ones, the skeletons of natural products with a wide range of biological activities. The load of the photocatalyst is low and the oxidant is inexpensive and less toxic.

Synthesis of trifluoromethylthioesters from aldehydes via a visible light-promoted radical process.

We report herein an efficient, economical, and scalable trifluoromethylthiolation of aldehydes to generate trifluoromethylthioesters via a visible light-promoted radical process. The transformation features cheap reagents, simple operation, a broad substrate scope, and especially no metal involved in the reaction. Trifluoromethylthiolations of several complex aldehyde-containing bioactive compounds have been realized; thus the approach has the potential to be an important tool for the late-stage functionalization of advanced synthetic intermediates and bioactive molecules, and should have many applications in medicinal chemistry.

Synthesis of difluoromethylselenoesters from aldehydes via a radical process.

Difluoromethylselenoester compounds, another important kind of organoselenium compounds, are reported herein for the first time. They can be efficiently synthesized from aldehydes and BnSeCF2H. The synthetic method features mild reaction conditions, broad substrate scope, good tolerance of functional groups, and importantly, no metal is involved in the reaction.

Synthesis of (E,E)-Dienones and (E,E)-Dienals via Palladium-Catalyzed γ,δ-Dehydrogenation of Enones and Enals.

A new strategy for the synthesis of conjugated (E,E)-dienones and (E,E)-dienals via a palladium-catalyzed aerobic γ,δ-dehydrogenation of enones and enals has been developed. The method can be employed in the direct and efficient synthesis of various (E,E)-dienones and (E,E)-dienals, including non-substituted α-, ß-, and γ- and/or δ-substituted (E,E)-dienones and (E,E)-dienals. The protocol is featured by the ready accessibility and elaboration of the starting materials, good functional group compatibility, and mild reaction conditions. Furthermore, the reaction is of complete E,E-stereoselectivity and uses molecular oxygen as the sole clean oxidant.

Dehydrogenative ß-Arylation of Saturated Aldehydes Using Transient Directing Groups.

An unprecedented cross-dehydrogenative-coupling (CDC) reaction of saturated aldehyde ß-C-H with arenes to form cinnamaldehydes via the cleavages of four C-H bonds has been developed. The reaction possesses complete E-stereoselectivity for the C═C double bond. The protocol is featured by atom and step economy, mild reaction conditions, and convenient operation.

Direct Dehydrogenative Arylation of Benzaldehydes with Arenes Using Transient Directing Groups.

The utilization of the transient directing strategy into the direct oxidative dehydrogenative arylation of aldehydes with arenes was reported for the first time. Featured by mild reaction conditions, good functional group compatibility, and great regioselectivity, the method should find broad applications in new medicine and material development and discovery processes.

Synthesis of Hydrazines via Radical Generation and Addition of Azocarboxylic tert-Butyl Esters.

A new chemistry of azo compounds that is a radical generation and addition in situ of azocarboxylic tert-butyl esters to synthesize hydrazines has been described. The protocol provides a novel strategy for the synthesis of various hydrazines. The advantages of the transformation include broad substrate scope, benign conditions, and convenient operation.

Synthesis of Difluoromethylthioesters from Aldehydes.

Difluoromethylthioester compounds are yet another important kind of organofluorine compound and are reported here for the first time. They can be efficiently synthesized from various aldehydes. The synthetic method features mild reaction conditions, good tolerance of functional groups, broad substrate scope, and importantly, no metal is involved in the reaction. The approach has the potential to become an important tool for the late-stage functionalization of advanced synthetic intermediates, and should have many applications in medicinal chemistry.

[Effect of methylphenidate on c-Fos expression in parvalbumin interneurons of juvenile rat frontal cortex].

The etiology of attention-deficit hyperactivity disorder (ADHD) has been generally linked to the decrease in cortex activity, as well as to the reduction in dopamine (DA) and norepinephrine (NE) levels. Methylphenidate (MPH; Ritalin) is the most commonly prescribed medication for ADHD. It has been determined that MPH acts primarily on the dopaminergic and noradrenergic systems through blockade of DA and NE transporters, thereby increasing the concentrations of these neurotransmitters in the brain to correct the attention deficits and hyperactivity. In addition, MPH has been proposed to increase the excitability of pyramidal neurons and the overall activity of cortex. However, the effect of MPH on the activity of interneurons is lack of investigation. Here, by using immunohistochemistry technique, we examined c-Fos expression in parvalbumin (PV)-expressing interneurons of frontal cortex of rats (28-day-old) at 1 h after a single MPH infusion (1 or 8 mg/kg; s.c.). We analyzed the c-Fos expression in the medial orbitofrontal cortex (MO), ventral orbitofrontal cortex (VO), and lateral orbitofrontal cortex (LO) subregions of orbitofrontal cortex (OFC), as well as the prelimbic cortex (PrL) and infralimbic cortex (IL) subregions of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) after MPH infusion. Our data showed that MPH increased c-Fos expression in MO, VO and LO, and the c-Fos expression in PV-expressing interneurons elevated significantly in MO, VO, but not in LO. Meanwhile, the increases of c-Fos expression in PrL and IL, as well as in PV-expressing interneurons of these two regions, were only induced by 1 mg/kg MPH, but not 8 mg/kg. Both 1 and 8 mg/kg MPH dramatically increased c-Fos expression in ACC, especially, in PV-expressing interneurons of ACC as well. In conclusion, acute systemic injection of MPH significantly increases the c-Fos expression in PV-expressing interneurons of the OFC, PFC and ACC.

[Growth Differentiation Factor 15 Inhibits Elevated Expression of Matrix Metalloproteinase 1 Induced by Pooled Serum in Patients with Coroanry Artery Ectasia].

OBJECTIVE: To observe the effects of coroanry artery ectasia (CAE) patients' pooled serum on the main proteinases and extracellular matrix (ECM) synthesis and explore whether the growth differentiation factor 15(GDF 15) can regulate the characteristic changes induced by CAE patients' pooled serum. METHODS: Serum samples were collected from 32 CAE patients, 30 patients with coronary heart disease (CHD), and 31 subjects with normal coronary arteries (CON) and then mixed in the same volumes by groups. Then human umbilical vein smooth muscle cells were cultured with the media containing 25% pooled serum. After having been disposed, proteinase system and ECM synthesis system were detected in the cell and culture media samples. GDF15 or GDF15 antibodies was added into the 25% pooled serum in each group to observe if GDF 15 could impact the characteristic changes induced by CAE patients' pooled serum. RESULTS: The expression of matrix metalloproteinases (MMP) 1 mRNA in CAE group was significantly higher than CON group (P=0.002) and CHD group (P=0.000), the secretory MMP1 protein and total MMPs activity in culture media were also upregulated in CAE group (both P<0.01). After adding GDF 15 into the culture media (GDF15+CAE group), the MMP1 mRNA ,secretory MMP1 protein, and total MMPs activity were significantly lower than CAE group (all P<0.01), while in the GDF15 antibody+CAE group, the MMP1 mRNA and total MMPs activities were significantly higher than in GDF15+CAE group (both P<0.01), but the secretory MMP1 protein was not different from GDF 15+CAE group (P>0.05). CONCLUSION: The vascular smooth muscle cells may participate in the CAE process mainly by regulating MMPs system but not the elastase 2 or ECM synthesis system, and GDF15 may be an compensatory factor to prohibit the over-destruction of coronary ECM induced by MMPs.

Silver-Catalyzed Coupling of Two C sp(3)-H Groups and One-Pot Synthesis of Tetrasubstituted Furans, Thiophenes, and Pyrroles.

Silver-catalyzed coupling of two C sp(3)-H groups to form 1,4-diketones have been developed for the first time. The resultant ketones then undergo cyclization to synthesize tetrasubstituted furans, thiophenes, and pyrroles from benzyl ketone derivatives in a one-pot reaction process. This highly-efficient synthetic method, which utilizes air as the terminal oxidant and readily accessible starting materials, displays a wide substrate scope and broad functional-group tolerance.

Copper-catalyzed radical reaction of N-tosylhydrazones: stereoselective synthesis of (E)-vinyl sulfones.

A new chemistry of hydrazines that is a copper-catalyzed radical reaction to synthesize vinyl sulfones from readily available N-tosylhydrazones has been described. The protocol provides a novel strategy for the synthesis of various vinyl sulfones including α, ß-disubstituted ones and terminal ones. The advantages of the transformation include excellent E stereoselectivity, broad substrate scope, low cost of reagents, and convenient operation. A novel and efficient one-pot synthesis of alkynes from N-tosylhydrazones has been achieved. The studies provide important complementary approaches for the syntheses of vinyl sulfones and alkynes.