Transition Metal-Catalyzed Amination / Oxidation of Ynamides for the Synthesis of 2H-Pyrroles / α- Functionalized Amides

近年来炔酰胺成为有机化学领域高度关注的研究热点之一。同时，炔酰胺化学也取得了很大的研究进展。炔酰胺分子中氮原子的供电子效应使得其碳碳三键高度极化，因而使得炔酰胺在反应过程中显示出较高的活性和优秀的区域选择性。 本论文研究结果包括三个部分：（1）金催化与路易斯酸催化的组合应用：2H-吡咯类化合物的简易合成方法研究；（2）锌催化的炔烃氧化反应来合成α-硫氰酸酯酰胺类化合物；（3）钪催化的炔烃氧化反应来合成α-烷氧基酰胺类化合物。 论文第一部分研究了金催化与路易斯酸催化的组合应用来合成多取代2H-吡咯类化合物。该反应的亮点在于：通过金催化与路易斯酸组合催化的异噁唑和炔酰胺的反应，以高收率得到了重...In recent years, ynamide has become one of the hotspots of organic chemistry. At the same time, ynamide chemistry has also made great progress. The electron-donating ability of the nitrogen of ynamide strongly polarizes the triple bond, which allows for exceptionally high levels of reactivity and regioselectivities. The research contents of this thesis include three parts: (1) combination of gol...学位：工学硕士院系专业：化学化工学院_化学工程学号：2062014115143

多目标多测度数据空间抽样方法

社会问卷调查往往需要针对多目标测度不同类型的数据,而传统的抽样方法主要针对单目标对象,且数据类型为数值型数据。本研究以厦门岛出行调查为例,调查问卷包含了住区特征、居民社会经济状况、就业情况、出行方式、出行目的与时间等方面的指标,提出了以变异度模型为主的新方法。以厦门岛住区居民出行所带来的能耗问题收集的少量先验问卷信息以及历史数据为基础,通过模型表征测度不同类型变量的空间变异性,将其作为空间分层的依据从而完成抽样布点方案,评价精度通过抽样方差进行。结果表明:(1)综合多种因素分层可以灵活地解决调查中涉及类别数据以及数值型数据的问题,将影响抽样问题的各类型因素体现到样点空间布点方案中,扩大三明治空间抽样的应用范围;(2)三明治空间抽样各层样点的分布以及容量受层变异度值(相当于方差)的影响,但其样本容量并不是简单随着区域的层变异度值的增大而增大,空间抽样样本容量同时受到多个因素的影响,其地理空间的大小也是其中一个影响因素;(3)变异度模型成功地量化了各种类型数据,通过少量的预调查得到更详细的抽样方案,其抽样精度为0.0002,样本容量35,满足了问卷调查的目标需求并将抽样样本容量控制在合理的范围之内。国家自然科学基金项目(41671444)~

Facile Synthesis of 2H-Pyrroles: Combination of Gold Catalysis and Lewis Acid Catalysis

报道了利用金催化与铜催化相结合合成5-氨基-2H-吡咯的方法.首先通过均相金催化异恶唑与炔酰胺反应生成α-亚胺金卡宾中间体,再经[3+2]环加成反应合成并分离出5-氨基-3H-吡咯,然后通过铜催化的去酰基化和基团迁移反应来实现3H-吡咯向2H-吡咯的转化.该方法不但操作简单、反应条件温和、官能团兼容性良好,而且还能进行克量级放大.这项研究为合成具有重要生物活性的5-氨基-2H-吡咯化合物提供了广谱实用的合成方法.A two-step synthesis of 5-amino 2H-pyrroles using gold and copper catalysis was presented. Firstly, 5-amino 3H-pyrroles were synthesized by gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles via α-imino gold carbene intermediate. The following Lewis acid-triggered decarbonylation and group migration results in the formation of 5-amino 2H-pyrroles. Other notable features of this method include the simple procedure, the mild reaction conditions and compatibility with a broad range of functional groups. Thus, this protocol provides a practical and general solution for the synthesis of 5-amino 2H-pyrroles. Accordingly, isoxazole 2(2.0 equiv., 0.6 mmol) and Ph3 PAu NTf2(5 mol%) were added to a suspension of the ynamide 1(1.0 equiv., 0.3 mmol) in DCM(3.0 m L) at room temperature. The reaction mixture was then stirred at r.t. and the progress of the reaction was monitored by TLC. The reaction typically took 2 h. Upon completion, the mixture was quenched with pyridine, concentrated and purified by chromatography on silica gel, using an eluent of petroleum ether/ethyl acetate(5/1, V/V), to afford 3H-pyrrole 3. Then, 3H-pyrrole 3 and Cu(OTf)2(10 mol%) were dissolved in DCM(3 m L) and stirred at room temperature for 6 h. The residue was purified by column chromatography on silica gel, using an eluent of petroleum ether/ethyl acetate(3/1, V/V), to afford the desired 2H-pyrrole 4. Under this condition, a variety of differently substituted ynamides 1 and isoxazoles 2 work well to provide the corresponding 2H-pyrroles 4a~4l in moderate to good overall yields. But N-(4-methoxybenzyl)-N-(phenylethynyl)methanesulfonamide 1a reacts with 4-(3-bromophenyl)-3,5-dimethylisoxazole 2d poorly under this condition, affording product 4h in only 33% yield. These results indicate that this method has certain universality, but the reaction is influenced by the substituents to some extent. Notably, the scalability and preparative utility of the developed methodology was exemplified by the fact that the desired product 4a was obtained without a significant loss in yield when the reaction was scaled up to 5 mmol. Also a plausible mechanism is proposed and we tend to believe that the reaction is featured by an α-imino gold carbene intermediate.国家自然科学基金(No.21272191);; 福建省杰出青年科学基金(No.2015J06003);; 国家基础科学人才培养基金(No.J1310024)资助~

利用导电涂膜直接电解海水法防护生物腐蚀 1.模拟和测量技术

基于电化 学微探针 和微弱 信号检测 技术， 采用 四电 极体 系、双恒 电 位仪、锁相 相 关测定系统 以及三维 微调装 置建立模 拟和测量 系统，将 首次实 现对利 用导 电涂 膜直 接电 解海 水法 防护生物腐 蚀中微 米尺度内 痕量 Ｃｌ Ｏ － 浓度 的测量．本 文报道 了模拟和 测量实验 的阶段 性进展

Design of new type of medical infrared temperature measuring instrument

目的:针对市场现有的测温仪的弊端,设计一种新型医用红外测温仪。方法:采用红外线温度传感器采集人体温度,以HT67F5640芯片为主控制器,通过A/D转换把检测的人体温度显示在液晶显示器(liquid crystal display,LCD)上。该仪器设计的电路包括主控制电路、电源电路、红外温度传感器电路、LCD驱动电路、按键电路、报警电路等;软件部分包括主程序,AD采集、LCD显示、蜂鸣器报警以及按键扫描等子程序。结果:该医用红外测温仪测量体温速度快、精度高、重复性好,医务人员反应良好。结论:该测温仪功耗低、使用方便、稳定性高、便于携带、各项参数优越,可以实现患者体温的快速检测。Objective To design a new type of medical infrared temperature measuring instrument.Methods The data on human body temperature were collected by the infrared temperature sensor with HT67F5640 as the main controller,and then displayed on the LCD through the A/D conversion.The circuits of the instrument included power supply circuit,infrared temperature sensor circuit,LCD drive circuit,key circuit,alarm circuit,etc.The software involved in the main program,AD acquisition subroutine,environment temperature compensation subroutine,calibration mode subroutine,etc.Results The instrument gained advantages in speed,precision,repeatability and response from medical staffs.Conclusion The medical infrared thermometer behaves well in low power consumption,easy operation,high stability and portability and etc,and is very suitable for the rapid detection of the patient's temperature

Partitioning and transport of Polycyclic Aromatic Hydrocarbons in surface water from the downstream to Lingdingyang of Pearl River

为了研究河口水体中多环芳烃(PAHS)的相态分布、传输特征及其变化趋势,本文沿珠江下游至河口对表层水体PAHS进行采样分析。结果显示,16种优控PAHS的总浓度为(17.50~168.35)ng/l,平均83.40 ng/l,其中溶解相为(3.76~83.60)ng/l,颗粒相为(1.59~84.75)ng/l。PAHS浓度自下游至伶仃洋有波动降低的趋势,该趋势受陆源的持续输入、浮游植物的吸附吸收以及海水的稀释作用等因素的共同影响;PAHS组成及两相分配的变化主要受控于输入特征、悬浮颗粒物和黑碳吸附以及盐析效应等环境因子。荧蒽和芘的分配系数kP自珠江下游至伶仃洋的逐渐下降也说明了海水的稀释显著降低了悬浮颗粒物对PAHS的吸附。另外,特征化合物比值沿程的变化不仅指示了PAHS在广州段水体中较长的停留时间,也说明了虎门河口存在持续的PAHS输入。利用主因子分析和多元线性回归的方法,指示出煤和木材燃烧以及机动车排放是该区域表层水体PAHS污染的最主要来源,约贡献了80%的PAHS输入。In order to study the phase distribution,transport and variation of polycyclic aromatic hydrocarbons(PAHs),surface water samples were collected along the downstream to Lingdingyang of Pearl River.The total concentrations of 16 US EPA PAHs ranged from 17.50 ng /L to 168.35 ng /L with the average of 83.40 ng /L [dissolved phase:(3.76 ~ 83.60) ng /L,particle phase:(1.59 ~ 84.75) ng /L].The declining trend of PAHs concentrations was showed from the downstream to Lingdingyang under the influence of the terrestrial continuous inputs,phytoplankton adsorption and seawater dilution.Variations of PAHs composition and partitioning were controlled by input pathway,adsorption of suspended particulate matters(SPM) and black carbons and the salting out effect.The partition coefficients of Fluo and Py decreased gradually indicated that the water dilution affected the adsorption of SPM to PAHs.In addition,the trend of Fluo /(Py + Fluo) suggested the longer retention time of PAHs in downstream of Pearl River and the continuous inputs of PAHs in Humen estuary.The principal factor analysis indicated the coal and wood combustion and vehicle emissions were the major sources of PAHs in the surface water,which contributed almost 80%of PAHs input.国家自然科学基金项目(41276066

健康小鼠进食绣球菌对腹腔巨噬细胞分泌肿瘤坏死因子α的影响

测定健康小鼠进食绣球菌对腹腔巨噬细胞分泌肿瘤坏死因子α(TNF-α)的影响.SPF级Balb/C健康小鼠分组进食普通饲料、分别含绣球菌饲料、干品、浸汁饮水或其添加物组合、分别含酵母β-葡聚糖饲料、浸汁饮水或其添加物组合;进食一定时间后,分离腹腔巨噬细胞,使用含质量分数10%胎牛血清的RPMI1640培养液培养,TNF-α试剂盒检测上清液中的TNF-α质量浓度.结果表明,强化进食绣球菌组合(绣球菌饲料+干品+浸汁)的小鼠与对照组或酵母β-葡聚糖组合(酵母β-葡聚糖饲料+浸汁)小鼠相比,体质量不升反降;分离的腹腔巨噬细胞培养6 d,酶联免疫吸附测定技术检测上清液TNF-α,其质量浓度远高于其它两组.研究提示,强化绣球菌进食组合能够提高健康小鼠免疫力,并可能有利于控制体质量.福建省自然科学基金资助项目(2013J01394);;吴阶平医学基金会临床科研项目(320.6750.15231);;空军军医大学国重开放课题(CBSKL201729);;福建省中医药大学校管课题(XB2015077

Determination of Estrogenic Compounds in Water of Jiulong River Using Polar Organic Chemical Integrative Sampler

极性有机物一体化采样器(POCIS)作为富集水体中有机物的新型采样技术,可以反映目标物在被测水体中的时间权重浓度,因此在环境监测中是对主动采样方式的重要补充.本研究采用POCIS进行了4种固醇类雌激素化合物(雌酮、雌二醇、雌三醇及雌炔醇)的富集动力学,以及温度和目标物浓度对POCIS富集雌激素影响的实验室模拟研究.结果表明,POCIS对目标化合物的富集放置时间7 d内呈现显著的线性关系(r2≥0.988 1,P12%),随着温度的升高,目标化合物在POCIS上的采样速率减小.而目标物浓度对POCIS富集没有显著的影响(rSd 12%).As for different concentrations of target compounds,the sampling rate was not affected by the concentrations( RSD < 5%).After laboratory experiments,an environmental field study was performed in Jiulong River.The results showed that there was a relatively good correlation between the measured and calculated values( r2= 0.720 9,P < 0.001).It demonstrated that POCIS can be used in aquatic field systems.近海海洋环境科学国家重点实验室访问学者基金项目; 海洋公益性行业科研专项(201105013

Over One Hundred Year Sedimentary Record of Polycyclic Aromatic Hydrocarbons in the Andaman Sea, Malaysia

[摘要]：采用GCPMS 分析研究了马来西亚海域安达曼海兰卡威岛邻近海域沉积物柱样(WC02) 中多环芳烃(PAHs) 组成与含量的 垂直分布特征, 结合210Pb定年, 重现了该海域近百年来PAHs 的沉积历史( 1898~ 2004 年) . 研究表明, PAHs 在整个沉积剖面( 0 ~ 56 cm) 的含量介于1312~ 6011 ng# g- 1 之间( 平均值2814 ng# g- 1) , 所分析的PAHs 中以菲、萘、等化合物为主, 与当地周边海 域相比污染程度较轻. 在20 世纪20 年代以前, 沉积物中多环芳烃含量较低, 基本代表当地环境的本底值, 即多环芳烃主要来 源于天然物质的输入; 20 年代以后PAHs 的总量有所上升, 并在20 世纪60 年代和80 年代出现了2 个峰值, 表明这段时间内多 环芳烃的陆源输入特征比较明显, 也反映了人类活动在20 世纪20 年代后开始对该海域产生一定的影响. 采用母体、高低环 PAH 比值对沉积物柱样中PAHs 的来源进行分析, 表明该海域沉积物受到燃料不完全燃烧产物污染为主、并伴有石油类污染, 这与马来西亚西海域周边地区的人类活动( 工农业生产、进出口、海上活动等) 密切相关, 同时也受到马六甲海峡繁忙的海上 交通运输影响. 对沉积物柱样污染历史进行分析, 表明PAHs 含量的阶段性变化与该地区不同时期的人文活动和社会经济( 国 内生产总值) 的发展状况密切相关, 较好地反映了人类活动对环境的影响.[Abstract]:Polycyclic aromatic hydrocarbons (PAHs) in a sediment core collected from Langkawi Island of the Andaman Sea, Malaysia were determined by GCPMS, the vertical variations of concentration and distributions of PAHs were investigated. In combining with 210Pb2dating, the PAHs sedimentary record in the last 100 years was reconstructed and their possible sources were also discussed. The EPAH concentration ranged from 131226011 ng#g- 1 in the whole sedimentary section ( 0256 cm) with the dominant compounds of phenanthrene, naphthalene and perylene. The sediments contaminated to a lesser extent comparing with the surrounding waters. Before the 1920s, the concentrations of PAHs were considered to be the background level, which was implied from the natural inputs. The historical records of PAHs in the core showed that two distinct peaks which represented the input time of 1960s and 1980s, respectively, inferred that there were some relatively dramatically land2based inputs, and human activities leaded a clear impact to these waters during these periods. Furthermore, PAHs diagnostic ratios indicated that PAHs in the core sediments were mainly of pyrolytic origin ( combustion) , accompanied with minor petroleum origin. These were related with agriculture, industry, ocean import and export, and shipping activities in the surrounding regions. Meanwhile as the vital communication line, the marine transportation of the Strait of Malacca had influenced the environmental quality of the Andaman Sea. Meanwhile, based on the sedimentary record, PAHs concentrations were found to correlate positively with humanism activities and socioeconomic development (Gross Domestic Production) in the surrounding regions.国家自然科学基金项目( 20777060) ; 国家海洋局海洋三所 科技项目( 海三科2007021

基于肠肝轴研究栀子苷对非酒精性脂肪性肝炎大鼠的影响

目的观察栀子苷对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)大鼠的影响,并基于肠肝轴探讨栀子苷防治NASH的作用机制。方法将35只大鼠按随机数字表法分为5组,每组7只。即正常组、模型组、栀子苷组、盐酸吡格列酮组及培菲康组。除正常组外,其余28只大鼠采用高脂饮食16周建立大鼠NASH模型,在造模第9周开始给药,共治疗8周。第16周末经腹主动脉取血,生化法检测肝组织甘油三酯(TG)水平,苏木精-伊红(HE)染色观察肝组织、肠组织病理学变化。ELISA法检测肝组织白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)等炎症因子的表达水平。终点显色法检测血浆内毒素(LPS)含量。结果与正常组比较,模型组大鼠的肝组织显示出典型的NASH组织学特征,经栀子苷干预后,肝细胞脂肪变性、炎症浸润较模型组减轻。与正常组比较,模型组大鼠肠上皮细胞少量脱落,肠黏膜机械屏障受损。经栀子苷干预后,回肠黏膜结构完整,未见明显肠上皮细胞脱落。与正常组比较,模型组大鼠脂肪重量、肝湿重、肝指数、肝脏TG含量、血浆LPS水平、肝组织IL-1β、IL-6、TNF-α等炎症因子水平均有不同程度增高(P<0.01)。经干预后,栀子苷组大鼠脂肪重量、肝湿重、肝指数、肝脏TG含量、血浆LPS水平、肝组织IL-1β、IL-6、TNF-α等炎症因子水平均较模型组有不同程度的下降(P<0.05,P<0.01)。结论栀子苷能明显改善大鼠肠黏膜组织结构,保持肠黏膜屏障的完整性,显著降低血浆LPS水平,显著降低NASH大鼠肝组织IL-1β、IL-6、TNF-α等炎症因子的表达。提示栀子苷治疗NASH的作用机制与调节肠肝轴、改善肠黏膜屏障、减少内源性LPS产生、降低炎症因子表达有关。国家自然科学基金资助项目(No.81673660)2017、2018厦门大学大学生创新创业训练课题(No.2017X0547; No.201810384230