含噻唑环结构的新型吡唑酰胺类化合物的合成与杀虫活性研究

为了探索新的吡唑酰胺活性物质,基于吡螨胺的结构,将噻唑环通过酰胺键同吡唑环相连,合成了18个未见文献报道的吡唑酰胺类化合物,通过~1H NMR, ~(13)C NMR和元素分析等手段确证了其结构.生物活性测试研究显示,所有目标化合物在500μg/mL时对粘虫都有100%的杀虫活性. 7个目标化合物在500μg/mL时对蚜虫具有70%～100%的防治效果.同时, 3个目标化合物在500μg/mL时对朱砂叶螨显示出40%～50%的防效.     

新型含硫羰基结构的Aspernigerin衍生物的合成及抑菌活性研究

基于天然产物Aspernigerin的结构特征,设计合成了一系列含有硫羰基结构的新型四氢喹啉类化合物.化合物结构均经过~1H NMR, ~(13)C NMR, HRMS确证,用X射线单晶衍射测定了(E)-3-(4-氟苯基)-1-[4-(1,2,3,4-四氢喹啉-1-羰基)哌嗪-1-基]丙-2-烯-1-酮(5j)的晶体结构.并对目标化合物的抑菌活性进行了研究.离体真菌抑制活性结果表明,部分目标化合物显示出较好的生物活性,其中(E)-1-[4-(1,2,3,4-四氢喹啉-1-羰基)哌嗪-1-基]-3-(邻甲苯基)丙-2-烯-1-酮(5b)对苹果腐烂病菌的抑制活性(EC_(50)=3.04μg/mL)优于对照药剂氟酰胺(EC_(50)=9.16μg/mL),可作为二级先导进行进一步的优化研究.     

芳酰胺类衍生物的合成及蛋白酪氨酸磷酸酶1B和含SH2结构域蛋白酪氨酸磷酸酶2抑制活性研究

为拓展含串联二芳酰胺结构的蛋白酪氨酸磷酸酶1B(PTP1B)抑制剂的化学空间,将其中的联苯二胺结构单元简化为芳基酰胺结构单元,设计并合成了18个芳酰胺类化合物.活性测试结果表明,部分芳酰胺衍生物对PTP1B和含SH2结构域蛋白酪氨酸磷酸酶2(SHP2)显示了一定强度的抑制活性.其中化合物3c[IC_(50)=(5.13±0.21)μmol/L]对PTP1B显示了中等强度的抑制活性,并且对其他亚型[T细胞蛋白酪氨酸磷酸酶(TCPTP)、含SH2结构域蛋白酪氨酸磷酸酶1(SHP1)和SHP2]显示了一定的选择性.有意思的是,化合物12对SHP2显示了中等强度的抑制活性[IC50=(7.47±1.26)μmol/L],对PTP1B、TCPTP以及SHP1显示了2倍的选择性,为发现新型选择性SHP2抑制剂提供了新的骨架类型.     

新型含噁唑单元的吡唑酰胺衍生物的合成及其生物活性

为了寻找具有良好生物活性的吡唑酰胺化合物,基于氯虫苯甲酰胺的结构,在吡唑环的5-位引入取代噁唑环单元,合成出了一系列新型吡唑酰胺,利用~1H NMR, ~(13)C NMR和元素分析对其目标产物的结构进行了确证.生测结果表明,所有目标化合物在500μg/mL时对粘虫均显示出较好的杀虫活性(致死率≥90%). 5个化合物在100μg/mL时对粘虫的防治效果可达90%～100%,3个化合物在100μg/mL时对苜蓿蚜的杀死率为90%～100%.另外,2个化合物在500μg/mL时对朱砂叶螨的防效可达80%～100%.     

(E)-1,5-二苯基-2-烯-1-戊酮的合成及生物活性研究

(E)-1,5-二苯基-2-戊烯-1-酮(I)是从瑞香狼毒(Stellera chamaejasme L.)中分离得到的天然产物,能有效防治重要农业害虫蚜虫.以价廉易得的苯乙酮为起始原料,经过4步反应合成化合物I,所得目标产物结构经过1HNMR,IR和元素分析确证.并探讨了反应温度和溶剂对产物顺反比例的影响.生物活性测试结果表明,化合物I对桃蚜(Myzus persicae)具有较强的杀蚜活性,其LC50为178.96μg/mL.     

含磺酰胺结构的1,3,4-噁二唑砜类化合物的设计、合成及抗菌活性研究

为了寻找新型抗菌剂,采用活性亚结构拼接,设计合成了23个含磺酰胺结构的1,3,4-噁二唑砜类化合物,并对其抗菌活性进行了测试.在100μg/m L浓度下,大多数化合物对水稻细菌性条斑病菌(Xanthomonas oryzae pv.oryzicola)和水稻白叶枯病菌(Xanthomonas oryzae pv.oryzae)表现出优异的离体抗菌活性.除N-((5-(丙基磺酰基)-1,3,4-噁二唑-2-基)甲基)-4-(三氟甲基)苯磺酰胺(18)外,所有化合物对水稻细菌性条斑病菌的半数有效浓度(EC₅₀)值为1.3～22.5μg/mL所有化合物对水稻白叶枯病菌的EC₅₀为1.1～32.7μg/m L,均优于对照药剂叶枯唑(84.1和71.4μg/mL)和噻菌酮(122.1和84.0μg/m L).此外,4-氟-N-((5-(甲基磺酰基)-1,3,4-噁二唑-2-基)甲基)苯磺酰胺(4)可以通过抑制胞外多糖(EPS)的产生、生物膜的形成以及改变细胞膜的通透性和细胞表面形态,从而抑制水稻细菌性条斑病菌和水稻白叶枯病菌的正常生长.     

N-氮杂环甲氧基-O-(4-芳氧基苯基)乳酸酰胺的合成与除草活性

以A8169为先导,设计并合成了12个新型的N-氮杂环甲氧基-O-(4-芳氧基苯基)乳酸酰胺化合物,其结构经1H NMR,13C NMR,LC/MS和IR确证.初步生物活性测定结果表明,化合物在2250 g/ha剂量下,对单子叶杂草马唐(Digitaria sanguinalis)、稗草(Echinochloa crus-galli)、狗尾草(Setaria viridis)等均具有100%的除草活性,进一步活性筛选发现,(R)-(+)-N-[(2-氯噻唑-5-基)甲氧基]-O-[4-((6-氯喹喔啉-2-基)氧基)苯氧基]乳酸酰胺(2f)除草活性(马唐IC50=6.8g/ha,稗草IC50=6.6 g/ha)远高于同类商品化除草剂炔草酯和先导化合物A8169.     

基于昆虫nAChR选择性的新型低蜂毒苯乙酰腙类似物的筛选和优化(英文)

近年来,越来越多的新烟碱类杀虫剂由于对蜜蜂存在的安全问题陆续被欧盟和美国禁用.本研究通过虚拟筛选结合生物活性评价的双重策略实现骨架跃迁,发现苯乙酰腙类化合物VS-04对大豆蚜表现出较好的杀虫活性,且化合物VS-04和蜜蜂烟碱型乙酰胆碱受体(nAChRs)的作用模式与传统的吡虫啉显著不同.新合成的苯乙酰腙类似物3c和3e在500μg/mL浓度下对大豆蚜致死率为70%,具有中等活性.更重要的是,通过蜜蜂毒性研究确证化合物3c和3e对蜜蜂表现出极低的急性接触毒性,其LD_(50)值(30.35和124.4μg/bee)比吡虫啉(0.019μg/bee)低3～4个数量级.通过化合物3m晶体结构确证化合物3c的酰腙结构以L型低能构象指向蜜蜂受体α亚基,进一步预示其低蜂毒特征.基于化合物3e进一步优化得到的化合物4f和4g对大豆蚜表现出更好的致死活性,其LC_(50)值分别是83.42和66.44μg/mL,优于化合物3e (LC_(50)=147.30μg/mL).这一研究将有利于以不同昆虫nAChR结构为靶标发现环境友好的新烟碱替代物.     

新型杂环查尔酮衍生物的合成及其杀虫活性研究

以含杂环的醛和氨基苯乙酮以及酰氯为原料,通过Claisen-Schmidt缩合反应和酰氯的氨解反应合成了21个新的杂环查尔酮衍生物.以蚕豆蚜(Aphis craccivora)和菜青虫(Pieris rapae)为靶标,对合成化合物的杀虫活性进行了实验室生测.结果显示,大部分化合物都对这两种害虫有一定的毒杀活性.其中,化合物2l对蚕豆蚜的半致死浓度(LC_(50))为1.6μg/m L,毒杀效果优于吡虫啉(LC_(50)为1.8μg/m L),1b、1f、2j、2n对蚕豆蚜的毒杀效果也和吡虫啉接近;化合物1f和2m对菜青虫的LC_(50)分别为6.6μg/m L和8.5μg/m L,毒杀效果比高效氯氰菊酯(LC50为9.2μg/m L)更好.     

含1,3,4-噻二唑和吡唑的酰胺衍生物的合成和抗肿瘤活性研究（英文）

以苯乙酮和草酸二乙酯为原料,设计并合成了一系列含有1,3,4-噻二唑和吡唑的新型酰胺衍生物A1～A26,通过~1H NMR,~(13)C NMR,IR,ESI-MS和HRMS等多种手段对其结构进行了表征.通过噻唑蓝(MTT)方法评估了这些化合物对人肝癌细胞(HepG2)和人胃癌细胞(MGC803)体外抗肿瘤活性的表现.实验结果表明,以5-氟尿嘧啶作为阳性对照药物(IC_(50)=0.0787μmol/mL),化合物A1 (IC_(50)=0.0695μmol/mL),A2 (IC_(50)=0.0682μmol/mL)和A3 (IC_(50)=0.0753μmol/mL)对HepG2细胞表现出相似的抑制作用.值得注意的是,化合物A1对MGC803细胞表现出较强的抑制作用(IC_(50)=0.0420μmol/mL),远比阳性对照药物5-氟尿嘧啶(IC_(50)=0.0820μmol/mL)优异.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.