Synthesis of Ring-Fused 1-Benzazepines via [1,5]-Hydride Shift/7-Endo Cyclization Sequences.

Synthesis of 1-benzazepines has been achieved via a [1,5]-hydride shift/7-endo cyclization sequence. The focus of this research is a direct transformation of 2-(aryl)cyclopropane 1,1-diester derivatives into 1-benzazepines using a cyclopropane moiety as the hydride acceptor in internal redox reactions.

Enantioselective one-pot synthesis of ring-fused tetrahydroquinolines via aerobic oxidation and 1,5-hydride transfer/cyclization sequences.

Enantioselective organocatalytic synthesis of tetrahydroquinolines has been achieved via an aerobic oxidation and a 1,5-hydride transfer/cyclization sequence. The feature of this research is a one-pot transformation of 3-arylprop-2-en-1-ol derivatives into tetrahydroquinolines using a Ru(VII)-catalyzed aerobic oxidation and highly efficient internal redox reactions. The synthetically useful ring-fused tetrahydroquinoline derivatives are obtained in moderate yields and high levels of enantioselectivity.

Suppression of TRIF-dependent signaling pathway of toll-like receptors by (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine.

Toll-like receptors (TLRs) play an important role in the recognition of microbial pathogens and induce innate immune responses. The recognition of microbial components by TLRs triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-ß (TRIF)-dependent downstream signaling pathways. Previously, we synthesized (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), which contains a nitrovinyl-phenyl and pyrrolidine. To evaluate the therapeutic potential of NVPP, its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[I:C]) was examined. NVPP inhibited LPS or poly[I:C]-induced activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), and the phosphorylation of IRF3, as well as inhibiting the activation of interferon-inducible genes such as interferon inducible protein-10 (IP-10). These results suggest that NVPP can modulate TRIF-dependent signaling pathways of TLRs, potentially resulting in effective therapeutics for chronic inflammatory diseases.

Suppression of inducible nitric oxide synthase expression induced by Toll-like receptor agonists by (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine.

Toll-like receptors (TLRs) recognize many pathogen-associated molecular patterns and induce innate immunity. TLR signaling pathways induce the activation of various transcription factors, such as nuclear factor-κB (NF-κB), leading to the induction of pro-inflammatory gene products, such as inducible nitric oxide synthase (iNOS). Here, we investigated the effect of an (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), previously synthesized in our laboratory, on inflammation by modulating NF-κB activation and iNOS expression induced by TLR agonists in murine macrophages. NVPP suppressed NF-κB activation and iNOS expression induced by lipopolysaccharide (TLR4 agonist), polyriboinosinic polyribocytidylic acid (TLR3 agonist), and macrophage-activating lipopeptide 2kDa (TLR2 and TLR6 agonist). All the results suggest that NVPP is suitable for development as a new anti-inflammatory drug.

Variation of ADM1 by using temperature-phased anaerobic digestion (TPAD) operation.

The objective of the study was to examine the application of the Anaerobic Digestion Model No. 1 (ADM1) developed by the IWA task group for mathematical modelling of anaerobic process. Lab-scale temperature-phased anaerobic digestion (TPAD) process were operated continuously, and were fed with co-substrate composed of dog food and flour. The model platform implemented in the simulation was a derivative of the ADM1. Sensitivity analysis showed that k(m.process) (maximum specific uptake rate) and K(S.process) (half saturation value) had high sensitivities to model components. Important parameters including maximum uptake rate for propionate utilisers (k(m.pro)) and half saturation constant for acetate utilisers (K(S.ac)) in the thermophilic digester and maximum uptake rate for acetate utilisers (k(m.ac)) in the mesophilic digester were estimated using iterative methods, which optimized the parameters with experimental results. Simulation with estimated parameters showed good agreement with experimental results in the case of methane production, uptake of acetate, soluble chemical oxygen demand (SCOD) and total chemical oxygen demand (TCOD). Under these conditions, the model predicted reasonably well the dynamic behavior of the TPAD process for verifying the model.

Sequential modeling of fecal coliform removals in a full-scale activated-sludge wastewater treatment plant using an evolutionary process model induction system.

We propose an evolutionary process model induction system that is based on the grammar-based genetic programming to automatically discover multivariate dynamic inference models that are able to predict fecal coliform bacteria removals using common process variables instead of directly measuring fecal coliform bacteria concentration in a full-scale municipal activated-sludge wastewater treatment plant. A sequential modeling paradigm is also proposed to derive multivariate dynamic models of fecal coliform removals in the evolutionary process model induction system. It is composed of two parts, the process estimator and the process predictor. The process estimator acts as an intelligent software sensor to achieve a good estimation of fecal coliform bacteria concentration in the influent. Then the process predictor yields sequential prediction of the effluent fecal coliform bacteria concentration based on the estimated fecal coliform bacteria concentration in the influent from the process estimator with other process variables. The results show that the evolutionary process model induction system with a sequential modeling paradigm has successfully evolved multivariate dynamic models of fecal coliform removals in the form of explicit mathematical formulas with high levels of accuracy and good generalization. The evolutionary process model induction system with sequential modeling paradigm proposed here provides a good alternative to develop cost-effective dynamic process models for a full-scale wastewater treatment plant and is readily applicable to a variety of other complex treatment processes.

Analysis and application of ADM1 for anaerobic methane production.

An anaerobic model for the serum bottle test was developed and analyzed with sensitivities of stoichiometric and kinetic parameters to the components in order to establish a basis for appropriate application of the model. Anaerobic glucose degradation in a serum bottle was selected as an example. The anaerobic model was developed based on the anaerobic digestion model no. 1 (ADM1), which had five processes with 17 kinetic and stoichiometric parameters. Sensitivity analysis showed that the yield of product on the substrate (f) has high sensitivities to model components, and that the methane concentration was the most sensitive component. Important parameters including yield of product on the substrate (f), yield of biomass on the substrate (Y), and half-saturation values (K) were estimated using genetic algorithms, which optimized the parameters with experimental results. The Monod maximum specific uptake rate (k) was, however, so strongly associated with the concentration of biomass, that values could not be estimated individually. Simulation with estimated parameters showed good agreement with experimental results in the case of methane production. However, there were some differences in acetate and propionate concentrations.