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铜催化酮类化合物的氧膦化反应与烯烃的磺酰胺化反应和熊果酸衍生物的设计与合成研究
有机膦、硫化合物在功能性材料、农药、合成及药物化学领域应用十分广泛。因此,发展高效、操作简便及环境友好的方法合成含膦、硫的有机化合物具有十分重要的意义。β-羰基氧膦化合物是一类非常重要的含膦有机化合物,它是著名的Horner-wittig反应的关键中间体,可以用来合成许多重要的结构骨架,如:取代的环丙烷、烯烃和羰基化合物。传统的合成β-羰基氧膦化合物的方法存在反应条件苛刻、反应原料不易得或者原子经济性差等缺点。近年来,我们研究组和其他课题组相继报道了不同条件下的烯烃、炔烃、烯酸和炔酸等不饱和烃的氧膦化反应。然而,酮类化合物作为一种廉价易得的反应原料,尚未有文献报道以它为底物合成β-羰基氧膦化合物方法。我们课题组在前期烯烃氧膦化研究工作的基础上,发展了以酮类化合物为原料,过渡金属铜催化氧气参与的合成β-羰基氧膦的新方法。该方法首次实现了酮类化合物直接转化为β-羰基氧膦化合物,丰富了合成β-羰基氧膦化合物的方法学,具有如下优点:底物适用范围广、反应条件温和、反应时间短和操作简单。通过自由基捕获实验证明了该反应经历了自由基历程,18O同位素标记实验证明了产物羰基中的氧原子来自于氧气。LC-MS实验检测到了该反应的关键中间体,进一步验证了我们推测的反应机理的合理性。磺酰胺结构单元许是多具有生物活性的分子的特征结构之一,降血压药呋塞米(Furosemide)、降血糖药格列吡嗪(Glipizide)和抗菌药磺胺甲噁唑(Sulfamethoxazole)都含有磺酰胺结构单元。烯基磺酰胺是一类具有特殊结构的磺酰胺类化合物,它可以作为有机反应的重要中间体合成许多具有生物活性的杂环类化合物。传统的合成烯基磺酰胺的方法需要强碱条件或者预先制备反应底物,因此,存在反应条件苛刻、操作复杂和底物适用范围窄等缺点。近年来,应用过渡金属催化的方法合成原本需要苛刻反应条件才能制备的化合物是有机化学的研究热点之一。在本论文中,我们课题组发展了过渡金属铜和配体催化的芳基烯烃和胺基磺酰氯之间的磺酰胺化反应。在反应中,溴化亚铜作为催化剂,1,10-菲啰啉作为配体,二氯甲烷为溶剂。该催化反应体系具有如下优点:条件温和、反应时间短和操作简便。机理研究表明该反应经历了自由基加成及消除反应过程。肿瘤是严重威胁人类健康的疾病之一,临床已有的治疗方法存在毒副作用大,容易产生耐药性等缺点。寻找能够作用于多个靶点和多条通路且对身体有整体调节作用的抗癌药物是解决这些问题的有效手段。天然产物数量庞大,且大多具有副作用小和具有多种生理活性的特点,对于治疗肿瘤这种复杂系统疾病具有很大优势。熊果酸是广泛存在于自然界中的属于五环三萜类的天然产物,有多种生物活性及药理作用,如抗肿瘤、抗病毒、抗炎、降糖、肝保护和胃保护等。我们实验室在筛选能够杀伤和抑制肿瘤细胞增殖的活性天然产物时,发现熊果酸具有诱导肿瘤细胞凋亡的活性。但是,熊果酸的水溶性差,导致其生物利用度低,类药性差。为了进改善其成药性,基于基本的药物设计原理,我们对熊果酸3-位羟基和28-位羧基进行了结构修饰改造共合成了48个结构新颖的化合物
自愈合功能材料及其愈合机理研究
基于生物体损伤愈合的灵感和材料耐久可靠的要求,自愈合材料的概念应运而生。自愈合材料可以修复其在外界环境因素作用下产生的局部创伤或微裂纹,故大大延长了材料的使用寿命,提高了材料使用过程中的安全稳定性。在过去的十几年里,自愈合材料的研究取得了令人瞩目的进展。但是,研究中大多数是结构型自愈合材料,而功能型自愈合材料的工作还鲜有报道。因此,构筑一种功能性强,愈合速度快,机械性能和功能特性可同时修复,并且可实现多次愈合的功能材料仍是一个挑战。本论文正是着眼于这种自愈合功能材料的构筑、设计、机理以及应用进行了初步探索。1. 基于主客体识别的自愈合导电弹性体。基于环糊精主客体识别作用,我们利用表面接枝环糊精(β-CD)的单壁碳纳米管(SWCNT)与含有客体基团金刚烷(Ad)的甲基丙烯酸羟乙酯(HEMA)进行组装,然后将包合物和HEMA单体在四氢呋喃溶剂中共聚,成功制备了具有自愈合功能的导电弹性材料(PHEMA-SWCNT)。研究表明:通过β-CD与Ad之间的主客体组装,SWCNT与HEMA形成了交联的三维网状结构,材料表现出优良的弹性和机械性能。由于SWCNT均匀密集堆积相互缠结形成导电通路,弹性材料呈现出良好的导电性能。当材料受损伤时,断面处存在大量游离的主体和客体基团,两断面重新接触后即可发生主客体相互作用导致材料自愈合。实验表明,三次重复愈合后,材料的机械性能恢复50%以上,导电性能恢复90%以上。此外,该材料在湿度传感和接近感应领域亦有潜在的应用价值。2. 基于环糊精主客体识别的自愈合材料愈合机理。通过构筑五种不同类别的复合物材料,我们深入探讨了基于环糊精主客体识别构筑自愈合材料的愈合机理。研究表明,主客体相互作用在材料愈合过程中扮演着重要角色。材料的愈合效率与愈合条件、材料的吸湿性能、分子链的运动以及主客体之间的包合能力密切相关。研究结果为基于主客体识别的自愈合材料设计提供了有意义的理论指导和有示范的参考价值。3. 定向排列的自愈合电纺纤维/膜及其电磁波吸收性能。我们以电场作为成丝驱动力,利用静电纺丝技术制备了定向排列的自愈合纤维,累积纺丝时间可以得到定向排列的聚合物薄膜,SWCNT在纤维/薄膜中沿着轴向定向排列。当薄膜受到较小损伤时,可以在温和的条件下实现微裂纹的自愈合。此外,聚合物中定向排列的SWCNT表现出特异的电磁波性能,使该薄膜材料具有良好的电磁波吸收特性,在军事、国防科技和航空航天等领域有潜在的应用价值。4. 基于氢键构筑自愈合水凝胶。基于氢键构筑自愈合材料的机理,我们通过2-氨基-4-羟基-6-甲基嘧啶(MIS)和甲基丙烯酸异氰基乙酯(ICEMA)的反应,合成了含有UPy基团的单体化合物(UPy-EMA),通过与甲基丙烯酸丁酯共聚得到含有UPy四重氢键的水凝胶。该水凝胶具有良好的机械性能和自愈合性能,并对其应用价值进行了初步探讨,有望用于生物化学、医学和生物传感等领域
小麦株高性状的全基因组关联分析
株高是影响小麦产量潜能的重要因素,且为多基因控制的数量性状。本研究利用高密度的小麦90K SNP芯片对西南麦区192份小麦品种(25份合成六倍体,80份地方品种,87份育成品种)进行株高性状的全基因组关联分析。结果共发现57个与株高相关的显著SNP位点,覆盖了19条染色体的50个区域。其中6个区域出现2个以上的SNP位点,10个位点至少在2个环境稳定表达。在四个环境中共同表达的4个SNP位点成簇分布在2A染色体2.2Mb的区段内,在该小麦群体中形成两种单倍型。进一步研究发现,其中2个SNP位点位于TaUBP24基因上,该基因编码一种泛素特异性的蛋白酶,且与株高显著相关。另外,6B染色体上的9个SNP位点成簇出现在前人已报道的qPh-6B位置。本研究中发现的基因及SNP位点将用于开发新的分子标记,并应用于小麦育种
细菌漆酶电子传递机制研究
漆酶(EC 1.10.3.2)是一类含铜离子的氧化酶,从底物吸收电子并传递给氧气,将氧气还原成水,属于多铜氧化酶家族,在高等植物、真菌、细菌和昆虫中都有发现。漆酶可以催化多种底物,包括邻(对)苯二酚、氮羟基化合物、苯胺和呈现还原性的有(无)机化合物等。漆酶的底物谱较广、催化效率高、还原氧气生成水,这些优点使得漆酶可以作为绿色环保的催化剂应用于多个领域。漆酶具有两个铜离子中心,单核铜离子中心从底物吸收电子,然后电子被传递到三核铜离子中心,氧气还原在三核铜离子中心完成,所以单核铜离子和三核铜离子中心存在偶联机制。本研究以细菌漆酶CotA为研究对象,通过比较CotA突变体与野生型蛋白的光谱学性质、催化活性和结构特征,探讨了两个铜离子中心的偶联机制
Evaluating the contribution of Yr genes to stripe rust resistance breeding through marker-assisted detection in wheat
Numerous stripe rust resistance genes have been identified from wheat, and new virulent races of Puccinia striiformis f. sp. tritici have also emerged in recent years. Deployment of diverse combinations of resistance genes is an efficient way to combat virulent evolution of strip rust pathogen. In this study, publically available molecular markers were used to identify the distribution of 36 Yr genes in 672 wheat accessions. The effectiveness of Yr genes individually and in combinations was also evaluated in field conditions. The result showed effective resistance of some recently applied genes, such as Yr15 and Yr65. It also showed the lost efficacy of some once widely used genes, such as Yr9 and Yr10. Moreover, significant additive effects were observed in some gene combinations, such as Yr9 + Yr18 and Yr30 + Yr46. Proper deploying of Yr genes and utilizing the positive interactions will be helpful for durable resistance breeding in wheat
基于定量蛋白质组学分析迭鞘石斛对肺癌细胞的抑制作用及机理
以基于SILAC(Stable isotope labeling with amino acids)的定量蛋白质组学为主要研究方法,通过精确定量蛋白质含量并进行差异分析,从蛋白层面系统研究迭鞘石斛(Dendrobium denneanum)乙醇提取物对人肺癌细胞A549的影响.结果发现迭鞘石斛乙醇提取物对A549细胞具有明显的抑制作用,其在降低细胞增殖速率的同时导致细胞发生死亡,24 h和48 h时的抑制率分别为35.05%和59.08%.定量蛋白质组学实验发现迭鞘石斛乙醇提取物引起A549细胞中392个蛋白质的含量出现明显下调.功能分析显示下调蛋白主要包括细胞物质和能量代谢相关蛋白,如RNA代谢与蛋白质合成、糖类代谢、脂类代谢、嘧啶与嘌呤代谢等.同时大量与细胞抵抗内源及外界不利刺激和损伤相关的蛋白,如具有氧化还原、分子伴侣、DNA修复、蛋白降解与修复等功能的蛋白含量也出现明显的下调.本研究通过定量蛋白质组学实验从全细胞蛋白层面系统解释了迭鞘石斛的抑癌作用机理,可促进石斛抗癌机理的进一步研究和石斛源抗癌新药的开发工作
Polystichum zhijinense (subg. Haplopolystichum; Dryopteridaceae), a new cave species of Polystichum from Guizhou, China
A new fern species, Polystichum zhijinense, a member of P. subg. Haplopolystichum (Dryopteridaceae), is described and illustrated from Guizhou Province in Southwest China. Polystichum zhijinense is somehow similar to P. fengshanense in having pinnae oblong and entire or shallowly repand (not aristate-spinulose on the margin), but differs in the shape of the pinna apex, the morphology of microscales, and the sorus distribution. Polystichum zhijinense was found at a cave entrance and is currently known from one population only and thus is classified as Critically Endangered (CR) following IUCN Red List criteria
PAKISTANI ANTI-MASTITIS MEDICINAL PLANTS AND THEIR SCIENTIFIC VALIDATION AGAINST MULTIDRUG RESISTANCE MASTINOGEN STAPHYLOCOCCUS AUREUS
Mastitis is an infectious disease of livestock affecting agricultural economy especially in developing countries. Present review was designed to gather literature about the traditional uses of Pakistani anti-mastitis plants and their In vitro background against a common multidrug resistant mastitis causing bacteria Staphylococcus aureus. Different online search engines were used use to collect data such as Web of Science, Scopus, Google Scholar and Pub Med.Traditional healers of Pakistan used 38 plants for the treatment of mastitis in buffaloes and cows. Zingiberaceae, Asteraceae, Rutaceae and Solanaceae (3 plants each) were the most preferred plant families while the roots, fruits and seeds were the most commonly used parts for the treatment of mastitis in Pakistan. Thirteen plants were reported to be evaluated for their antibacterial activities. Different extracts had shown good activities against S. aureus, however, ethanolic, aqueous and methanolic extracts shown greater inhibition zone (10-25mm). Variety of phytochemical classes was identified from in-vitro tested plants such as saponins, glycosides, alkaloids, carbohydrates flavonoids and terpenoids. Literature review showed that S. aureus is resistant (60-100%) to commonly used antibiotics against mastitis. In Pakistan large number of plants are being used against mastitis but most of the regions are yet to explore. Moreover, many reported plants were found to be active against S. aureus while large number of plants is still unexplored. There is a dire need to expedite detailed ethnopharmacological studies on unexplored anti-mastitis plants for the replacement of current drugs with new plant based drugs
Polystichum alluvium (subg. Haplopolystichum; Dryopteridaceae), a new cave species from Guizhou, China, with reference to new distribution records of P. leveillei
A new fern species, Polystichum alluvium, a member of P. subg. Haplopolystichum (Dryopteridaceae), is described from Guizhou Province in Southwest China. Polystichum alluvium is similar to P. lanceolatum in having small habit and subcoriaceous pinnae, but the former has oblanceolate laminae with basal pinnae strongly contracted toward lamina base, deltoidovate and sessile pinnae, and very short spinules on acroscopic pinna margins or no spinules, while the latter has lanceolate laminae with basal pinnae not contracted toward lamina base, oblong and petiolate pinnae, and long spinules on acroscopic pinna margins. Polystichum alluvium was found from the alluvial bottom of a karst cave at an elevation of 1410 m with humid and shady conditions and is currently known from one population with ca. 50 plants in western Guizhou. It is classified as Critically Endangered (CR) following IUCN Red List criteria. We also expanded the distribution of P. leveillei to southern-central Guizhou based on our new collections
Phosphorous Application Improves Drought Tolerance of Phoebe zhennan
Phoebe zhennan (Gold Phoebe) is a threatened tree species in China and a valuable and important source of wood and bioactive compounds used in medicine. Apart from anthropogenic disturbances, several biotic constraints currently restrict its growth and development. However, little attention has been given to building adaptive strategies for its conservation by examining its morphological and physio-biochemical responses to drought stress, and the role of fertilizers on these responses. A randomized experimental design was used to investigate the effects of two levels of irrigation (well-watered and drought-stressed) and phosphorous (P) fertilization treatment (with and without P) to assess the morphological and physio-biochemical responses of P. zhennan seedlings to drought stress. In addition, we evaluated whether P application could mitigate the negative impacts of drought on plant growth and metabolism. Drought stress had a significant negative effect on the growth and metabolic processes of P. zhennan. Despite this, reduced leaf area, limited stomatal conductance, reduced transpiration rate, increased water use efficiency, enhanced antioxidant enzymes activities, and osmolytes accumulation suggested that the species has good adaptive strategies for tolerating drought stress. Application of P had a significant positive effect on root biomass, signifying its improved water extracting capacity from the soil. Moreover, P fertilization significantly increased leaf relative water content, net photosynthetic rate, and maximal quantum efficiency of PSII under drought stress conditions. This may be attributable to several factors, such as enhanced root biomass, decreased malondialdehyde content, and the up-regulation of chloroplast pigments, osmolytes, and nitrogenous compounds. However, P application had only a slight or negligible effect on the growth and metabolism of well-watered plants. In conclusion, P. zhennan has a strong capability for drought resistance, while P application facilitates and improves drought tolerance mostly through physio-biochemical adjustments, regardless of water availability. It is imperative to explore the underlying metabolic mechanisms and effects of different levels of P fertilization on P. zhennan under drought conditions in order to design appropriate conservation and management strategies for this species, which is at risk of extinction