The fluoranthene skeleton is a structure often found in natural products and fluorescent materials, and thus developing an operationally simple method for diversity-oriented fluoranthene synthesis is ...an important research topic in organic synthesis. However, existing synthetic methods require harsh reaction conditions or limited substrate applicability or both. Here, we report the room temperature synthesis of substituted fluoranthenes and azafluoranthenes through the cationic Rh(I)/H8-BINAP complex-catalyzed 2 + 2 + 2 cycloaddition using 1,8-dialkynylnaphthalenes. DFT calculations reveal that the H8-BINAP ligand stabilizes the intermediates, allowing the room temperature reaction. Among the substrates examined, 1,8-bis(phenylethynyl)naphthalene and diarylacetylenes show high reactivity, contrary to the reactivity predicted by their steric bulkiness. Theoretical and experimental mechanistic studies have demonstrated that the noncovalent interactions of the phenyl groups on both the substrates and the ligand accelerate the present sterically demanding reactions by stabilizing the transition states rather than inducing steric repulsions.
Organoboron and organosilicon compounds are used not only as synthetic building blocks but also as functional materials and pharmaceuticals, and compounds with multiple boryl and silyl groups are ...beginning to be used for these purposes. Especially in drug discovery, methodology providing easy stereoselective access to aliphatic nitrogen heterocycles bearing multiple boryl or silyl groups from readily available aromatic nitrogen heterocycles would be attractive. However, such transformations remain challenging, and available reactions have been mostly limited to dearomative hydroboration or hydrosilylation reactions. Here, we report the dearomative triple elementalization (carbo-sila-boration) of quinolines via the addition of organolithium followed by photo-boosted silaboration, affording the desired products with complete chemo-, regio-, and stereoselectivity. The reaction proceeds via the formation of silyl radicals instead of silyl anions. We also present preliminary studies to illustrate the potential of silaboration products as synthetic platforms.
A rhodium(III) complex bearing a 1,3-bis(ethoxycarbonyl)-substituted or an unsubstituted cyclopentadienyl ligand (CpE or Cp) significantly accelerates a variety of oxidative C–H bond ...functionalization reactions. However, the driving force of the acceleration compared with a conventionally used Cp*Rh(III) complex has not been elucidated. Herein, we performed density functional theory (DFT) calculations of the rhodium(III)-catalyzed oxidative C–H bond olefination and annulation reactions using Cp*, Cp, and CpE ligands, which revealed that the CpERh(III) complex stabilizes transition states of not only a C–H bond activation step but also rate-determining reductive elimination and insertion steps by strong orbital interactions. For the sterically demanding substrates, the less sterically hindered CpRh(III) complex can stabilize the transition states of the reductive elimination step more than the CpERh(III) complex. Moreover, the whole reaction pathways were calculated to elucidate the mechanism and selectivity of the oxidative 4 + 2 and 2 + 2 + 2 annulation reactions under cationic and neutral conditions, respectively.
It has been established that a newly developed cyclopentadienyl rhodium(III) CpARhIII complex, bearing an acidic secondary amide moiety on the Cp ring, is able to catalyze the ortho‐bromination of ...O‐phenyl carbamates with N‐bromosuccinimide (NBS) at room temperature. The presence of the acidic secondary amide moiety on the CpA ligand accelerates the bromination by the hydrogen bond between the acidic NH group of the CpA ligand and the carbonyl group of NBS.
Makes it faster! It has been established that a newly developed cyclopentadienyl rhodium(III) CpARhIII complex, bearing an acidic secondary amide moiety on the Cp ring, is able to catalyze the ortho‐bromination of O‐phenyl carbamates with NBS at room temperature. The hydrogen bond between the acidic NH group of the CpA ligand and the carbonyl group of NBS accelerates the bromination.
Screening for male-derived biological material from collected samples plays an important role in criminal investigations, especially those involving sexual assaults. We have developed a loop-mediated ...isothermal amplification (LAMP) assay targeting multi-repeat sequences of the Y chromosome for detecting male DNA. Successful amplification occurred with 0.5 ng of male DNA under isothermal conditions of 61 to 67 °C, but no amplification occurred with up to 10 ng of female DNA. Under the optimized conditions, the LAMP reaction initiated amplification within 10 min and amplified for 20 min. The LAMP reaction was sensitive at levels as low as 1-pg male DNA, and a quantitative LAMP assay could be developed because of the strong correlation between the reaction time and the amount of template DNA in the range of 10 pg to 10 ng. Furthermore, to apply the LAMP assay to on-site screening for male-derived samples, we evaluated a protocol using a simple DNA extraction method and a colorimetric intercalating dye that allows detection of the LAMP reaction by evaluating the change in color of the solution. Using this protocol, samples of male-derived blood and saliva stains were processed in approximately 30 min from DNA extraction to detection. Because our protocol does not require much hands-on time or special equipment, this LAMP assay promises to become a rapid and simple screening method for male-derived samples in forensic investigations.
cAMP responsive element binding protein (CREB)-regulated transcription coactivators (CRTCs) regulate gene transcription in response to an increase in intracellular cAMP or Ca2+ levels. To date, three ...isoforms of CRTC have been identified in mammals. All CRTCs are widely expressed in various regions of the brain. Numerous studies have shown the importance of CREB and CRTC in energy homeostasis. In the brain, the paraventricular nucleus of the hypothalamus (PVH) plays a critical role in energy metabolism, and CRTC1 and CRTC2 are highly expressed in PVH neuronal cells. The single-minded homolog 1 gene (Sim1) is densely expressed in PVH neurons and in some areas of the amygdala neurons. To determine the role of CRTCs in PVH on energy metabolism, we generated mice that lacked CRTC1 and CRTC2 in Sim1 cells using Sim-1 cre mice. We found that Sim1 cell-specific CRTC1 and CRTC2 double-knockout mice were sensitive to high-fat diet (HFD)-induced obesity. Sim1 cell-specific CRTC1 and CRTC2 double knockout mice showed hyperphagia specifically for the HFD, but not for the normal chow diet, increased fat mass, and no change in energy expenditure. Interestingly, these phenotypes were stronger in female mice than in male mice, and a weak phenotype was observed in the normal chow diet. The lack of CRTC1 and CRTC2 in Sim1 cells changed the mRNA levels of some neuropeptides that regulate energy metabolism in female mice fed an HFD. Taken together, our findings suggest that CRTCs in Sim1 cells regulate gene expression and suppress excessive fat intake, especially in female mice.
cAMP responsive element binding protein (CREB)-regulated transcription coactivators (CRTCs) regulate gene transcription in response to an increase in intracellular cAMP or Ca2+ levels. To date, three ...isoforms of CRTC have been identified in mammals. All CRTCs are widely expressed in various regions of the brain. Numerous studies have shown the importance of CREB and CRTC in energy homeostasis. In the brain, the paraventricular nucleus of the hypothalamus (PVH) plays a critical role in energy metabolism, and CRTC1 and CRTC2 are highly expressed in PVH neuronal cells. The single-minded homolog 1 gene (Sim1) is densely expressed in PVH neurons and in some areas of the amygdala neurons. To determine the role of CRTCs in PVH on energy metabolism, we generated mice that lacked CRTC1 and CRTC2 in Sim1 cells using Sim-1 cre mice. We found that Sim1 cell-specific CRTC1 and CRTC2 double-knockout mice were sensitive to high-fat diet (HFD)-induced obesity. Sim1 cell-specific CRTC1 and CRTC2 double knockout mice showed hyperphagia specifically for the HFD, but not for the normal chow diet, increased fat mass, and no change in energy expenditure. Interestingly, these phenotypes were stronger in female mice than in male mice, and a weak phenotype was observed in the normal chow diet. The lack of CRTC1 and CRTC2 in Sim1 cells changed the mRNA levels of some neuropeptides that regulate energy metabolism in female mice fed an HFD. Taken together, our findings suggest that CRTCs in Sim1 cells regulate gene expression and suppress excessive fat intake, especially in female mice.
We report a case of extracardiac rupture of the left Valsalva sinus aneurysm, which is an extremely rare and fatal lesion. The three drugs, clindamycin, ethambutol and rifampicin, had been ...administered for eleven years because of lung mycobacterium infection. An emergency surgery was performed because of cardiac tamponade. The left Valsalva sinus was entirely enlarged without an aneurysmal neck. The other Valsalva sinuses seemed to be almost normal. The aneurysmal wall adhered the pulmonary artery and the left atrium. The left descending and circumflex arteries independently originated from the aneurysmal wall. The left main trunk seemed to become a part of the aneurysmal wall. Additionally the intraoperative transesophageal echocardiography showed severe aortic regurgitation. The Bio-Bentall procedure was performed. The right coronary artery was reconstructed with the Carrel patch method and the saphenous vein grafts were anastomosed to the proximal portions of the left anterior descending and circumflex arteries, individually. On the thirty-third postoperative day, the patient was discharged uneventfully expect for the delayed sternal closure on the second postoperative day. Five and half years after surgy, the patient is living a normal life and rifampicin has been administered without any anticoagulation drugs.
A 67-year-old woman was referred to the department of orthopedic surgery with a chief complaint of sciatica on the lateral side of the right thigh. An abnormal vessel was pointed out and she was ...referred to our department. Enhanced CT showed the right persistent sciatic artery, type 2a of the Pillet-Gauffre classification, and its outer diameter was enlarged to 2.0 cm. The persistent sciatic artery communicated to the popliteal artery. The superficial femoral artery was hypoplastic and the profunda femoral artery was normal. VIABAHN was deployed into the persistent sciatic artery aneurysm from the right internal iliac artery to the upper third of the right thigh. The superior gluteal artery was preserved. After the procedure, she complained no sciatica. VIABAHN was patent and the aneurysm regressed without type II endoleak four years postoperatively.
Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive ...thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33
mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33
dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)
receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33
DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress.
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