松香含氮衍生物对小地老虎四龄幼虫的拒食活性及构效关系

采用叶碟浸叶法,研究了4种不同类型的松香含氮衍生物对小地老虎4龄幼虫的拒食活性。结果显示：脱氢枞胺对氯水杨醛Schiff碱（2i）和二氢枞酸异丙醇酰基硫脲（4b）较大地抑制了小地老虎4龄幼虫的取食,质量浓度1 g/L时2i和4b 24 h后的拒食率分别为86.12%和85.13%;脱氢枞胺对甲氧基苯甲醛Schiff碱（2b）、二氢枞酸2-羟甲基-1,3-丙二醇酰基硫脲（4c）和二氢枞酸呋喃酰基硫脲（4g）对小地老虎4龄幼虫具有较强的拒食活性,拒食率分别为52.04%、66.70%和50.48%。2i具有极低的拒食中质量浓度（AFC₅₀）,为0.04 g/L,2b、4b、4c和4g的AFC₅₀分别为0.66、0.25、1.47和0.69 g/L。脱氢枞胺（取代）苯甲醛Schiff碱和二氢枞酸酰基硫脲2类衍生物对小地老虎具有较强的拒食活性,甲氧基、氯原子和羟基对脱氢枞胺（取代）苯甲醛Schiff碱的拒食活性有明显的增强作用,二氢枞酸酰基硫脲衍生物中羟基的位置和个数对小地老虎4龄幼虫的拒食活性有明显的影响。脱氢枞酸酰胺和脱氢枞酸酰基硫脲衍生物对小地老虎4龄幼虫的拒食活性较弱,且其结构变化对小地老虎4龄幼虫的拒食活性影响较小。     

脱氢枞基含氮衍生物的抑菌活性研究

采用平板计数法研究了脱氢枞酸（1）和脱氢枞基含氮衍生物（脱氢枞胺（2）、脱氢枞酸酰胺衍生物（3a~3m）、脱氢枞胺（取代）苯甲醛Schiff碱衍生物（4a~4i））对6种病原真菌的抑制活性。结果表明：脱氢枞胺的抑菌活性优于脱氢枞酸，脱氢枞胺（取代）苯甲醛Schiff碱衍生物的抑菌活性优于脱氢枞酸酰胺衍生物。其中含卤原子的脱氢枞胺（对氯）水杨醛Schiff碱（4d）、脱氢枞胺（间氟）苯甲醛Schiff碱（4f）、脱氢枞胺（对氟）苯甲醛Schiff碱（4g）、脱氢枞胺（对氯）苯甲醛Schiff碱（4h）具有较强的抑菌活性，4h在质量浓度为180 mg/L时对灰葡萄孢、腐皮镰孢和芸苔链格孢的抑制率达100%，抑制率接近阳性对照物放线菌酮。进一步测定了脱氢枞胺（取代）苯甲醛Schiff碱衍生物4d、4f、4g和4h在不同质量浓度下对6种病原真菌的抑菌活性。结果发现4种化合物在不同质量浓度下对灰葡萄孢和芸苔链格孢均具有较好的抑制活性。化合物4f在22.5 mg/L时对6种病原真菌的抑制率最高，均大于95%，而4g在22.5 mg/L时的抑制率却最低，并且4h在45 mg/L时的抑制率较高，上述结果表明苯环上卤原子的取代位置和类型均会影响其在不同质量浓度下的抑菌活性和最佳抑菌活性的质量浓度。     

双脱氢枞基酰胺化合物的合成与体外抑菌活性

以脱氢枞酸为原料,在二氯甲烷溶剂中与二氯亚砜制备脱氢枞酰氯,再以无水碳酸钠作缚酸剂,脱氢枞酰氯与脱氢枞胺在四氢呋喃溶剂中回流生成双脱氢枞基酰胺化合物,收率46.3％.产物结构经核磁共振氢谱、碳谱及红外光谱确证.采用琼脂二倍稀释法对产物进行金黄色葡萄球菌、粪肠球菌、肺炎链球菌、铜绿假单胞菌、大肠埃希菌和阴沟肠杆菌6个菌种的体外抑菌活性实验,结果表明双脱氢枞基酰胺化合物对6个菌种的体外最低抑菌浓度(MIC)为8～128μg/mL,其中,对肺炎链球菌、阴沟肠杆菌的最低抑菌浓度(MIC)均为8μg/mL.     

新型含取代吡啶环的脱氢枞酸衍生物的合成和抗病毒活性研究

以脱氢枞酸为原料,依次通过酯化反应、乙酰化反应和四组分串联反应合成了11个新型含吡啶环的脱氢枞酸衍生物(化合物4a~4k)。利用FT-IR、1HNMR和ESI-MS对上述化合物进行了结构表征。采用四甲基偶氮唑蓝比色法(MTT比色法)测试了上述化合物对人体单纯疱疹病毒I型(HSV-1)的体外抗病毒活性。结果表明,该系列衍生物具有一定的抗病毒活性,对HSV-1的半数有效浓度EC50在10~25μmol/m L之间,化合物4g的抗病毒活性最强,其EC50为12.1μmol/m L。初步构效关系分析表明,将吡啶环结构引入到脱氢枞酸骨架中可以提高衍生物的抗病毒活性。     

新型β-酮亚胺化合物的合成

以二苯甲酰甲烷为原料,分别与邻甲基苯胺、邻氟苯胺和2,4-二氟苯胺反应,生成三种新型的β-酮亚胺化合物,反应条件温和,最高收率可达80%以上;产物通过1H NMR和元素分析进行表征。     

N,N—二乙基脱氢枞酰基氧化胺的合成及其性质研究

以脱氢枞酸为原料,经酰氯化、酰胺化和氧化三步反应合成了一种含松香基三元菲环结构的N,N—二乙基脱氢枞酰基氧化胺。采用正交实验方法对脱氢枞酸酰胺氧化的工艺条件进行了优化,制备反应的最佳工艺条件:反应时间12h,反应温度80℃,双氧水与酰胺的物质的量比为1.5:1,催化剂用量1.5%。利用红外光谱(FT-IR)和核磁(1H NMR)对目标产物结构进行表征。性能实验结果表明,用N,N—二乙基脱氢枞酰基氧化胺改性的天然沸石对刚果红具有较好的吸附效果。     

新型脱氢松香酰肼基硫脲的研究

以松香改性产品脱氢枞胺为原料,乙醚为溶剂,在-10～40℃下与二硫化碳(CS2)、N,N'-二环己基碳二亚胺(DCC)作用,合成脱氢松香异硫氰酸酯,最高产率为84.1%。然后以对甲苯磺酰氯、苯磺酰氯、水合肼为原料,四氢呋喃为溶剂,在10～15℃下分别合成对甲苯磺酰肼(最高产率91.9%)和苯磺酰肼(最高产率96%)。最后,松香异硫氰酸酯分别与对甲苯磺酰肼、苯磺酰肼反应,乙醇为溶剂,于60～80℃条件下回流搅拌,合成了対甲苯磺酰肼基脱氢枞氨基硫脲和苯磺酰肼基脱氢枞氨基硫脲,最大收率均大于60%。所合成的化合物经红外光谱、核磁共振谱等表征分析,证实是一种未见报道的新化合物。     

2-苯胺-4-甲基-6-三氟甲基-1,3,5-三嗪衍生物的合成及其除草活性

合成了2苯胺1 ,3 ,5三嗪的一系列衍生物 ,并评价了它们的除草活性。首先研究了三嗪环上的取代 ,结果表明4甲基6三氟甲基衍生物显示高的除草活性 ,其次研究了2苯胺4甲基6三氟甲基1 ,3 ,5三嗪的苯环取代 ,结果表明苯环上的3或4卤素衍生物显示更高的除草活性。在盆载试验中表现高除草活性的2(3氯苯胺基)4甲基6三氟甲基1 ,3 ,5三嗪和2(4氯苯胺基)4甲基6三氟甲基1 ,3 ,5三嗪 ,其PET(光合电子通道)抑制活性也比除草剂西玛津和莠去津的高。     

间二酰胺类化合物NC-1的设计、合成及杀虫活性

为发现高效杀虫剂,采用活性药效基团融合策略,以2-氟-3-氨基苯甲酸甲酯和2-三氟甲基苯胺为起始原料,设计、合成了间二酰胺类化合物N-[2-溴-4-(全氟丙烷-2-基)-6-(三氟甲基)苯基]-3-[N-(氰甲基)苯甲酰胺基]-2-氟苯甲酰胺(NC-1),其结构经1HNMR、13CNMR和HRMS确证。初步的室内生物活性测试结果表明,化合物NC-1具有优异的杀虫活性,在质量浓度0.05 mg/L下对小菜蛾的致死率为96.67%,在质量浓度0.625 mg/L下对二化螟的致死率为93.33%。化合物NC-1可作为先导化合物或候选杀虫剂进行深入研究与开发。     

几种N-取代苯基马来酰亚胺单体的合成与表征

以马来酸酐、苯胺及其衍生物为主要原料合成了N-对甲苯基马来酰亚胺(NM PM I)、N-对氯苯基马来酰亚胺(NCLPM I)、N-对甲氧苯基马来酰亚胺(NM OPM I),产率可达85%以上。采用1H-NM R,13C-NM R和FT-IR等仪器对产物及中间产物马来酰胺酸的结构进行详细的表征。研究发现马来酰胺酸和马来酰亚胺苯环上不同的取代基,在1H-NM R谱图中,对HC=CH上质子峰的影响不大,而对苯环上质子峰却有影响,吸(供)电子基使苯环质子的化学位移向低(高)场移动;在13C-NM R谱图中,含强电负性(O、N、C l)的取代基使苯环上δc1低场移动,邻对位δc略向高场移动,取代基的电负性越大,位移也越大。     

松香多元酸对小地老虎的拒食活性研究

以松香为原料经Diels-Alder加成反应合成了松香多元酸如丙烯海松酸（APA）、富马海松酸（FPA）及马来海松酸（MPA）。采用浸叶法,研究了松香多元酸以及脱氢枞酸对小地老虎（Agrotis ypsilon）的拒食活性。结果显示：质量浓度为1g/L时,脱氢枞酸、丙烯海松酸、马来海松酸和富马海松酸对4龄小地老虎幼虫的24h拒食率分别为0.68%、78.41%、13.41%和79.94%,其中丙烯海松酸及富马海松酸对小地老虎的拒食活性较高,而马来海松酸对小地老虎的拒食活性较弱,脱氢枞酸几乎没有拒食活性。丙烯海松酸及富马海松酸对小地老虎的拒食中质量浓度（AFC₅₀）分别为0.04和0.06g/L,可以进行田间试验,进一步明确其在生产中的实际防治效果。     

Antifeedant and Termiticidal Activities of 6-Alkoxycoumarins and Related Analogs Against <Emphasis Type="Italic">Coptotermes formosanus</Emphasis> Shiraki

We synthesized 23 6-alkoxycoumarin derivatives, 20 of which are novel compounds. The structures of all compounds were confirmed by NMR, MS, and elemental analysis, and their antifeedant and termiticidal activities against Coptotermes formosanus Shiraki were examined. In a no-choice test, 6-(2-pentynyloxy)coumarin (2v), 6-(2-butynyloxy)coumarin (2u), 6-(2-octynyloxy)coumarin (2w), and 6-methoxycoumarin (2a), demonstrated high termiticidal activity at a concentration of 10 μmol. At a concentration of 5 μmol, 6-(2-butynyloxy)coumarin (2u) produced the highest mortality among the compounds tested. On the other hand, all of the 6-alkoxycoumarins showed antifeedant activity at both concentrations, except 6-octadecyloxycoumarin (2j) that was inactive at 5 μmol. Among the 23 compounds and the control, 6-ethoxycoumarin (2b), 6-isopropoxycoumarin (2d), and 6-isobutoxycoumarin (2f) exhibited the highest antifeedant activity with no mass loss (0.00%) at a concentration of 10 μmol. Our findings indicate that the presence of alkenyloxy and alkynyloxy groups was important for the termiticidal activity, while the incorporation of alkoxy groups with longer alkyl chains tended to reduce both the termiticidal and antifeedant activities. Furthermore, short chain alkoxy and arylalkoxy-substituted analogs showed good antifeedant activity, but methoxy groups on the benzene ring had a negative effect.     

木荷提取物对小菜蛾和菜青虫的拒食活性

室内测定了木荷甲醇提取物对小菜蛾、菜青虫3龄幼虫的拒食活性。结果表明，木荷树皮甲醇提取物对小菜蛾、菜青虫3龄幼虫的拒食活性最高。木荷树皮甲醇提取物在10g／L的质量浓度下，对小菜蛾3龄幼虫24h和48h的拒食率分别为94．27％和94．78％，拒食中浓度（AFC50）分别为2．7445g／L和1．5519g／L；对菜青虫3龄幼虫，在2g/L的质量浓度下，24h和148h的拒食率均达到100％，拒食中浓度（AFC50）分别为0．1053g／L和0．1488g／L。     

6‐Aryl and Heterocycle Quinazoline Derivatives as Potent EGFR Inhibitors with Improved Activity toward Gefitinib‐Sensitive and ‐Resistant Tumor Cell Lines

A group of novel anilinoquinazoline derivatives with variable aryl and heterocyclic substituents at position 6 were synthesized and tested for their EGFR‐inhibitory activity. Aryl and heterocyclic rings were attached to the quinazoline scaffold through different linkages such as imine, amide, and thiourea. Most of the aryl and heterocyclic derivatives showed potent inhibition of wild‐type EGFR with IC₅₀ values in the low nanomolar range. Among these, thiourea derivatives 6 a , 6 b and compound 10 b also retained significant activity toward the gefitinib‐insensitive EGFR^T790M/L858R mutant, displaying up to 24‐fold greater potency than gefitinib. In addition, cell growth inhibitory activity was tested against cancer cell lines with wild‐type (KB cells) and mutant EGFR (H1975 cells). Several compounds including 6 a were found to be more potent than the reference compound gefitinib toward both cell lines, as was the case for compound 10 b against H1975 cells. Therefore, compounds 6 a and 10 b in particular may serve as new leads for the development of inhibitors effective against wild‐type EGFR as well as gefitinib‐resistant mutants.     

Antitermite Activities of Coumarin Derivatives and Scopoletin from <Emphasis Type="Italic">Protium javanicum</Emphasis> Burm. f.

The antitermite (termiticidal and antifeedant) activity of Protium javanicum Burm. f. extract was investigated. The ethyl acetate fraction was active. Scopoletin (1), quercetin, and stigmasterol were isolated by bioassay-guided fractionation. Scopoletin had the highest activity among the three compounds. In order to investigate the structure-activity relationship (SAR) of the methoxy and hydroxy groups at the C-6 and C-7 positions of the coumarin skeleton, we synthesized several coumarin derivatives whose chemical structures are similar to scopoletin. Scopoletin exhibited the strongest termiticidal activity among the 10 compounds tested, followed by 6-methoxycoumarin (3), 6-hydroxycoumarin (7), and umbelliferone (8). All compounds except coumarin (9) showed antifeedant activity.     

Semisynthesis and Antifeedant Activity of New Derivatives of a Dihydro-β-Agarofuran from Parnassia wightiana

Five new derivatives (2–6) were semi-synthesized using compound 1, a dihydro-β-agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as the starting material by acylation, oxidation, reduction, esterification, and amination, respectively. Structures of 2–6 were confirmed by 1D- and 2D-NMR and HR-ESI-MS spectra. In addition, antifeedant activities of these compounds (1–6) were tested against the 3rd-instar larvae of Mythimna separata. Antifeedant effects of compounds 2 and 4 were greater than the parent compound 1 whereas other compounds exhibited low to no feeding deterrent effects against third instar M. separata larvae in lab bioassays. Therefore, our results suggest that acylated and reduced derivatives at C-8 and C-2, respectively, of 1 may improve the antifeeding effect. This preliminary information will be useful in designing new insect control agents against M. separata and other important pests.     

具有生物活性的喹啉类化合物的研究进展

概述了具有生物活性的喹啉类化合物的研究进展.根据结构特点分为4-羟基喹啉、6-羟基喹啉、8-羟基喹啉、4-胺(肼)基喹啉、喹啉酰胺、喹啉酮、二氯喹啉酸衍生物及其他等8类化合物,对其生物活性进行综述,介绍了部分农药品种的合成方法.     

1,2,3-三氮唑桥连水杨醛类席夫碱菊糖衍生物的合成及抑菌活性研究

先对菊糖C-6位的羟基进行溴代激活,形成易离去基团,再用叠氮基亲核置换易离去基团,最后将水杨醛类丙炔胺席夫碱中间体通过Huisgen-Click反应与叠氮代菊糖中间体桥连,得到1,2,3-三氮唑桥连水杨醛类席夫碱菊糖衍生物(4a~4c),通过红外光谱对其结构进行了表征,并测定其抑菌活性。结果表明,与菊糖相比,菊糖衍生物的抑菌活性明显提高,当浓度为1 000μg·mL-1时,化合物4a对黄瓜炭疽病菌(Colletotrichum lagenarium)、西瓜枯萎病菌(Fusarium oxysporium)和芦笋茎枯病菌(Phomopsis asparagi)的抑制率分别为66.7%、42.0%和58.1%。通过对菊糖进行针对性化学修饰,接入具有抑菌活性的基团,可以在一定程度上提高菊糖的抑菌活性,为进一步开发利用菊糖提供了依据。