Approaches to Asymmetric Catalysis Mediated by Ploymer-Supported and Homogeneous Organocatalysts

Aquesta tesi se centra en la síntesi d'organocatalitzadors, especialment els suportats en polímer, i la seva aplicació en diverses transformacions asimètriques. En el capítol II, s'ha desenvolupat una cicloaddició [4 + 2] eficient, altament regio- i estereoselectiva entre alquilidenpirazolones i enals mitjançant catàlisi via dienamina dirigida per enllaç d'hidrogen. El capítol III descriu un organocatalizador de tipus isotiourea suportat en poliestirè (PS), robust i d'alta eficiència per a una varietat de reaccions formals de cicloaddició [4 + 2]. A més, també es demostra la reciclabilitat del catalitzador d'isotiourea immobilitzat (11 cicles, TON acumulat de 76,8) i la seva aplicació en un procés de flux continu (sense disminució del rendiment o ee després de 18 h). En el capítol IV s'investiga una cicloaddició [8 + 2], d'ordre superior, asimètrica i periselectiva entre enolats d'amoni quiral i azaheptafulvens, promoguda per un catalitzador de isotiourea immobilitzat. Els productes de cicloaddició [8 + 2] resultants són susceptibles de derivatització via cicloaddició [4 + 2] completament regioselectiva amb dienòfils actius, per proporcionar productes policíclics d'una manera directa. L'últim capítol se centra en una reacció en cascada consistent en desoligomerització de paraldehid / reacció aldòlica creuada de benzaldehids pobres en electrons (o el complex η6-benzaldehid Cr (CO) 3), promoguda per un sistema catalític dual. A més, els productes obtinguts poden derivatizarse fàcilment a medicaments o intermedis de productes naturals.Esta tesis se centra en la síntesis de organocatalizadores, especialmente los soportados en polímero, y su aplicación en diversas transformaciones asimétricas. En el Capítulo II, se ha desarrollado una cicloadición [4 + 2] eficiente, altamente regio- y estereoselectiva entre alquilidenpirazolonas y enales mediante catálisis vía dienamina dirigida por enlace de hidrógeno. El Capítulo III describe un organocatalizador de tipo isotiourea soportado en poliestireno (PS) robusto y altamente eficiente para una variedad de reacciones formales de cicloadición [4 + 2]. Además, también se demuestra la reciclabilidad del catalizador de isotiourea inmovilizado (11 ciclos, TON acumulado de 76,8) y su aplicación en un proceso de flujo continuo (sin disminución del rendimiento o ee después de 18 h). En el capítulo IV se investiga una cicloadición [8 + 2], de orden superior, asimétrica y periselectiva entre enolatos de amonio quiral y azaheptafulvenos, mediada por un catalizador de isotiourea inmovilizado. Los productos de cicloadición [8 + 2] resultantes son asimismo susceptibles de derivatización vía cicloadición [4 + 2] completamente regioselectiva con dienófilos activos para proporcionar productos policíclicos de una manera directa. El último capítulo se centra en una reacción en cascada consistente en desoligomerización de paraldehído/reacción aldólica cruzada de benzaldehídos pobres en electrones (o el complejo η6-benzaldehído Cr(CO)3), promovida por un sistema catalítico dual. Además, los productos obtenidos pueden derivatizarse fácilmente a medicamentos o intermedios de productos naturales.This thesis focuses on the synthesis of organocatalysts, especially polymer-supported ones and their application in various asymmetric transformations. In Chapter II, an efficient, highly regio- and stereoselective [4+2] cycloaddition between alkylidene pyrazolones and enals through H-bond-directing dienamine catalysis has been developed. Chapter III describes a robust, highly efficient polystyrene-supported (PS) isothiourea organocatalyst in a variety of formal [4+2] cycloaddition reactions. In addition, recyclability of the immobilized isothiourea catalyst (11 cycles, accumulated TON of 76.8) and its application in continuous flow process (no decrease in yield or ee after 18 h) are also demonstrated. Chapter IV investigates an asymmetric periselective [8+2] higher-order cycloaddition between chiral ammonium enolates and azaheptafulvenes catalyzed by an immobilized isothiourea catalyst. The resulting [8+2] cycloadducts can also undergo completely regioselective [4+2] cycloaddition with active dienophiles to afford bridged polycyclic products in a straightforward manner. The last Chapter focuses on the cascade deoligomerization/cross-aldol reactions of electron-poor benzaldehydes or η6-benzaldehyde Cr(CO)3 complex with paraldehyde can be promoted by a dual catalytic system. Moreover, the obtained products can be easily transferred to medicinal drugs or natural product intermediates

Inhibition of Ascorbic Acid on Lotus Rhizome Polyphenol Oxidase: Inhibition Kinetics and Computational Simulation

Polyphenol oxidase(PPO) is widely known to be involved in enzymatic browning reaction in many fruits and vegetables including lotus rhizome with different catalytic mechanisms. In this study, the inhibitory effect and mechanisms of action of ascorbic acid (AA) on the lotus rhizome PPO were investigated using inhibition kinetics and computational simulation. The lotus rhizome PPO was extracted with PBS (pH 7.0), fractionated with ammonium sulphate, concentrated, and purified with DEAE-52(2.6×30 cm) and Sephadex G-75(2.6×60 cm) chromatography. The active fractions were pooled and the PPO activity was determined to be 2627.36Units/mg. AA exhibited inhibition on lotus rhizome PPO with residual activity of 13.79% at concentration of 0.08mM and IC50 of 0.045mM. Kinetic analyses determined by Lineweaver-Burk plots showed that ascorbic acid was reversible and competitive inhibitor to the enzyme. The 3D structure of the lotus rhizome PPO was simulated by SWISS-MODEL program and molecular docking was performed between PPO and its ligands (catehol and AA) by SYBYL-X 2.0. Simulation results showed that AA and catechol compete with the binding site of the PPO active center for its stronger affinity with the enzyme. In conclusion, the AA was established as a competitive inhibitor of lotus rhizome PPO, which provides a theoretical basis for it as an anti-browning agent in storage and preservation of lotus rhizome. Keywords: Lotus rhizome, Polyphenol oxidase, Computational simulation, Inhibition mechanis

Well pattern optimization based on StoSAG algorithm

The well pattern optimization in the oilfield is challenging and intricate work due to the heterogeneity of the permeability and viscosity. Traditionally, the well pattern optimization is conducted by comparing the results of several plans manually designed by the reservoir engineer, which is difficult to obtain the optimal well pattern. To address these challenges, a framework that integrates a reservoir simulator into the StoSAG algorithm is proposed. The well pattern operators proposed by Onwunalu and Durlofsy are applied to obtain the variations of the well pattern and used as the optimization variables. During the framework, the optimization variables are continuously adjusted by the StoSAG algorithm in order to obtain the optimal one which maximize the objective function value. The framework is applied to a synthetic reservoir. The results show that the StoSAG algorithm can be successfully applied in the well pattern optimization and remarkably improve the development effect. This method can be widely used in new oilfield development plan and offer reference for well pattern deployment.Cited as: Wang, S., Li, Z., Wang, S., Han, X. Well pattern optimization based on StoSAG algorithm. Advances in Geo-energy Research, 2018, 2(1): 103-112, doi: 10.26804/ager.2018.01.0

Mechanisms of reservoir pore/throat characteristics evolution during long-term waterflooding

Formation pore structure and reservoir parameters change continually during waterflooding due to sand production, clay erosion, and pressure/temperature variation, which causes great challenge in geological modeling and simulation. In this work, the XA Oilfield, a block with more than 20 years’ waterflooding history, is used as an example to better understand the fundamental evolution mechanisms of reservoir pore network characteristics over long time waterflooding. We performed a large number of core analyses and experiments to obtain formation parameters (e.g., permeability, porosity, relative permeability, and etc.) at different development stages. The comparison illustrates that reservoir permeability can not only decrease with clay plugging, but also increase by the detachment of fine particles and even the destruction of microscopic structure. We also observed that the point/line contacts among grains decreases, the pore network connectivity increases, the clay content reduces and the rock trends to be more hydrophilic with increasing water injection. Moreover, we developed a pore network model to simulate the variation of formation parameter. The model parameters are also compared and analyzed to get a qualitative understanding of the evolvement laws, which will provide a useful guidance for reservoir accurate modeling.Cited as: Wang, S., Han, X., Dong, Y., et al. Mechanisms of reservoir pore/throat characteristics evolution during long-term waterflooding. Advances in Geo-Energy Research, 2017, 1(3): 148-157, doi: 10.26804/ager.2017.03.0

Key candidate genes and pathways in T lymphoblastic leukemia/lymphoma identified by bioinformatics and serological analyses

T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL) is an uncommon but highly aggressive hematological malignancy. It has high recurrence and mortality rates and is challenging to treat. This study conducted bioinformatics analyses, compared genetic expression profiles of healthy controls with patients having T-ALL/T-LBL, and verified the results through serological indicators. Data were acquired from the GSE48558 dataset from Gene Expression Omnibus (GEO). T-ALL patients and normal T cells-related differentially expressed genes (DEGs) were investigated using the online analysis tool GEO2R in GEO, identifying 78 upregulated and 130 downregulated genes. Gene Ontology (GO) and protein-protein interaction (PPI) network analyses of the top 10 DEGs showed enrichment in pathways linked to abnormal mitotic cell cycles, chromosomal instability, dysfunction of inflammatory mediators, and functional defects in T-cells, natural killer (NK) cells, and immune checkpoints. The DEGs were then validated by examining blood indices in samples obtained from patients, comparing the T-ALL/T-LBL group with the control group. Significant differences were observed in the levels of various blood components between T-ALL and T-LBL patients. These components include neutrophils, lymphocyte percentage, hemoglobin (HGB), total protein, globulin, erythropoietin (EPO) levels, thrombin time (TT), D-dimer (DD), and C-reactive protein (CRP). Additionally, there were significant differences in peripheral blood leukocyte count, absolute lymphocyte count, creatinine, cholesterol, low-density lipoprotein, folate, and thrombin times. The genes and pathways associated with T-LBL/T-ALL were identified, and peripheral blood HGB, EPO, TT, DD, and CRP were key molecular markers. This will assist the diagnosis of T-ALL/T-LBL, with applications for differential diagnosis, treatment, and prognosis

Approaches to Asymmetric Catalysis Mediated by Ploymer-Supported and Homogeneous Organocatalysts

Aquesta tesi se centra en la síntesi d'organocatalitzadors, especialment els suportats en polímer, i la seva aplicació en diverses transformacions asimètriques. En el capítol II, s'ha desenvolupat una cicloaddició [4 + 2] eficient, altament regio- i estereoselectiva entre alquilidenpirazolones i enals mitjançant catàlisi via dienamina dirigida per enllaç d'hidrogen. El capítol III descriu un organocatalizador de tipus isotiourea suportat en poliestirè (PS), robust i d'alta eficiència per a una varietat de reaccions formals de cicloaddició [4 + 2]. A més, també es demostra la reciclabilitat del catalitzador d'isotiourea immobilitzat (11 cicles, TON acumulat de 76,8) i la seva aplicació en un procés de flux continu (sense disminució del rendiment o ee després de 18 h). En el capítol IV s'investiga una cicloaddició [8 + 2], d'ordre superior, asimètrica i periselectiva entre enolats d'amoni quiral i azaheptafulvens, promoguda per un catalitzador de isotiourea immobilitzat. Els productes de cicloaddició [8 + 2] resultants són susceptibles de derivatització via cicloaddició [4 + 2] completament regioselectiva amb dienòfils actius, per proporcionar productes policíclics d'una manera directa. L'últim capítol se centra en una reacció en cascada consistent en desoligomerització de paraldehid / reacció aldòlica creuada de benzaldehids pobres en electrons (o el complex η6-benzaldehid Cr (CO) 3), promoguda per un sistema catalític dual. A més, els productes obtinguts poden derivatizarse fàcilment a medicaments o intermedis de productes naturals.Esta tesis se centra en la síntesis de organocatalizadores, especialmente los soportados en polímero, y su aplicación en diversas transformaciones asimétricas. En el Capítulo II, se ha desarrollado una cicloadición [4 + 2] eficiente, altamente regio- y estereoselectiva entre alquilidenpirazolonas y enales mediante catálisis vía dienamina dirigida por enlace de hidrógeno. El Capítulo III describe un organocatalizador de tipo isotiourea soportado en poliestireno (PS) robusto y altamente eficiente para una variedad de reacciones formales de cicloadición [4 + 2]. Además, también se demuestra la reciclabilidad del catalizador de isotiourea inmovilizado (11 ciclos, TON acumulado de 76,8) y su aplicación en un proceso de flujo continuo (sin disminución del rendimiento o ee después de 18 h). En el capítulo IV se investiga una cicloadición [8 + 2], de orden superior, asimétrica y periselectiva entre enolatos de amonio quiral y azaheptafulvenos, mediada por un catalizador de isotiourea inmovilizado. Los productos de cicloadición [8 + 2] resultantes son asimismo susceptibles de derivatización vía cicloadición [4 + 2] completamente regioselectiva con dienófilos activos para proporcionar productos policíclicos de una manera directa. El último capítulo se centra en una reacción en cascada consistente en desoligomerización de paraldehído/reacción aldólica cruzada de benzaldehídos pobres en electrones (o el complejo η6-benzaldehído Cr(CO)3), promovida por un sistema catalítico dual. Además, los productos obtenidos pueden derivatizarse fácilmente a medicamentos o intermedios de productos naturales.This thesis focuses on the synthesis of organocatalysts, especially polymer-supported ones and their application in various asymmetric transformations. In Chapter II, an efficient, highly regio- and stereoselective [4+2] cycloaddition between alkylidene pyrazolones and enals through H-bond-directing dienamine catalysis has been developed. Chapter III describes a robust, highly efficient polystyrene-supported (PS) isothiourea organocatalyst in a variety of formal [4+2] cycloaddition reactions. In addition, recyclability of the immobilized isothiourea catalyst (11 cycles, accumulated TON of 76.8) and its application in continuous flow process (no decrease in yield or ee after 18 h) are also demonstrated. Chapter IV investigates an asymmetric periselective [8+2] higher-order cycloaddition between chiral ammonium enolates and azaheptafulvenes catalyzed by an immobilized isothiourea catalyst. The resulting [8+2] cycloadducts can also undergo completely regioselective [4+2] cycloaddition with active dienophiles to afford bridged polycyclic products in a straightforward manner. The last Chapter focuses on the cascade deoligomerization/cross-aldol reactions of electron-poor benzaldehydes or η6-benzaldehyde Cr(CO)3 complex with paraldehyde can be promoted by a dual catalytic system. Moreover, the obtained products can be easily transferred to medicinal drugs or natural product intermediates

Catalytic Asymmetric [8+2] Annulation Reactions Promoted by a Recyclable Immobilized Isothiourea

Higher‐order cycloaddition reactions constitute an efficient approach towards the construction of medium to large ring systems. However, enantioselective versions of these transformations remain scarce, which hampers their deployment in medicinal chemistry, or any other discipline in which homochirality is deemed crucial. Herein, we report a novel method for the production of enantiomerically enriched cycloheptatrienes fused to a pyrrolidone ring on the basis of an isothiourea‐catalyzed periselective [8+2] cycloaddition reaction between chiral ammonium enolates (generated in situ from carboxylic acids) and azaheptafulvenes. The resulting bicyclic compounds can be hydrogenated, but, most remarkably, they can also undergo completely regioselective [4+2] cycloaddition with active dienophiles to give architecturally complex polycyclic compounds in a straightforward manner

Study on Amplification Effect of Wind Turbine Blade Stopping Position on Vortex Induced Vibration of Tower

This project takes XX unit as the analysis object to study the first-order vibration wind speed of wind turbine under shutdown vibration. The vortex-induced vibration response is calculated and the displacement under resonant wind speed is calculated by fluid-solid coupling method. The above analysis techniques and methods are forward-looking and advanced in vibration characteristics of domestic wind turbines. On the basis of fluid dynamics analysis, the suppression measures are studied emphatically. Through the optimization and comparison of different inhibition schemes, the effect of inhibition measures was quantitatively analyzed. The analysis shows that the vibration characteristics of wind turbine with high flexible tower has its own particularity. The first order vibration probability and vibration displacement can be effectively reduced by pneumatic method and external measures