5-(3′-芳基-5′-噁唑烷酮基甲氧基)-3(2H)哒嗪酮类化合物的合成及生物活性

5-(3′-芳基-5′-噁唑烷酮基甲氧基)-3(2H)哒嗪酮类化合物的合成及生物活性;芳基噁唑烷酮基甲氧基哒嗪酮;合成;生物活性     

糖苷合成研究(ⅩⅩⅠ)2-N-(β-D-吡喃葡萄糖-1-基)-6-(4-卤代苯基)-3-哒嗪酮的合成

在相转移催化条件下,2,3,4,6-四-O-乙酰基-1-溴-1-脱氧-α-D-吡喃葡萄糖1与6-(4-卤代苯基)-3(2H)-哒嗪酮2反应,合成了4种新的哒嗪酮葡萄糖苷3;然后用干燥的氨气在0～-5 ℃下处理,得相应的2-N-(β-D-吡喃葡萄糖-1-基)-6-(4-卤代苯基)-3-哒嗪酮4. 这些化合物的结构经IR、1H NMR、13C NMR及元素分析所证实.     

4-卤-5-(4-甲基-2H-1-苯并-2-吡喃酮-7-氧基)-2-取代-3(2H)-哒嗪酮衍生物的合成和生物活性研究

通过4,5-二氯(溴)-3(2H)-哒嗪酮与7-羟基-4-甲基香豆素在CH3CN/K2CO3体系下的缩合反应,将具有生物活性的哒嗪酮环引入到苯并吡喃酮结构中,设计、合成了9个含哒嗪酮环的香豆素类化合物,其中8个为新化合物.所有化合物的结构均经NMR,MS和元素分析确证.初步生物活性测试结果表明:化合物4-氯-5-(4-甲基-2H-1-苯并吡喃-2-酮-7-氧基)-2-(4-硝基苯基)-3(2H)-哒嗪酮对黄瓜根部具有一定的抑制作用.     

哒嗪酮的乙酰胺类化合物的合成及生物活性

2-叔丁基-4-氯-5-羟基-哒嗪-3(2H)-酮(3)与相应的N-烷基或N,N-二烷基氯乙酰胺(4a-4l)反应,合成了2-叔丁基-5-[(N-烷基或N,N-二烷基乙酰胺)氧基]-4-氯-哒嗪-3(2H)-酮(1a-1l),生物活性测定结果表明部分化合物(1a-1l)具有杀虫活性。     

2-氨基-4-甲氧基氯代苯甲酸的合成研究

以2-氨基-4-甲氧基苯甲酸甲酯为原料,通过氯代反应,再分别通过酯水解反应得到化合物2-氨基-5-氯-4-甲氧基苯甲酸和2-氨基-3-氯-4-甲氧基苯甲酸。其中间体及产物结构经~1H NMR、~(13)C NMR和ESI-MS确证,并考察了最佳氯代反应条件。结果表明:物料配比为n(2-氨基-4-甲氧基苯甲酸甲酯)∶n(NCS)=1∶1. 2,反应溶剂为N,N-二甲基甲酰胺,反应时间为16 h,两种氯代产物2-氨基-5-氯-4-甲氧基苯甲酸甲酯和2-氨基-3-氯-4-甲氧基苯甲酸甲酯收率分别为47%和39%。     

3-O-(β-D-吡喃葡萄糖-1-基)-6-(4-卤代苯基)哒嗪的合成与表征

利用6-(4-卤代苯基)-3(2H)-哒嗪酮的银盐(2)与2,3,4,6-四-O-乙酰基-1-溴-1-脱氧-α-D-吡喃葡萄糖(3)发生Koenigs-knorr反应, 合成了3-O-(2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖-1-基)-6-(4-卤代苯基)哒嗪(4),4用干燥的氨气在0℃～-5℃下处理脱乙酰基保护基得相应的3-O-(β-D-吡喃葡萄糖-1-基)-6-(4-卤代苯基)哒嗪(5).其结构经元素分析,IR及1H NMR证实.     

糖苷合成研究(XXI)2-N-(β-D-吡喃葡萄糖-1-基)-6-(4-卤代苯基)-3-哒嗪酮的合成

哒嗪酮葡萄糖苷;相转移催化;糖苷合成研究(XXI)2-N-(β-D-吡喃葡萄糖-1-基)-6-(4-卤代苯基)-3-哒嗪酮的合成     

(E)-3-(1-亚胺基乙基)-5,5-二取代-4-甲氨基呋喃-2(5H)-酮的合成及其意外的杀虫活性（英文）

为了提高化合物对植物病原菌的杀菌活性及扩大多样性导向合成策略建立的分子库,以甲氨基替换3-(1-亚胺基乙基)-5,5-二取代-4-苯基呋喃-2(5H)-酮的苯基,设计合成了18个新颖的(E)-3-(1-亚胺基乙基)-5,5-二取代-4-甲氨基呋喃-2(5H)-酮,结构经过~1H NMR, ~(13)C NMR, HR-ESI-MS表征.(E)-3-(1-(4-甲氧基苄氧亚胺基)乙基)-4-甲氨基-1-氧杂螺[4.5]癸-3-烯-2-酮(5O)还经过X射线衍射表征.生物活性测试结果表明,所有化合物对测试的四种植物病原菌均未显示明显的活体杀菌活性,但是意外地发现多个化合物在600μg/mL浓度时对桃蚜、粘虫和小菜蛾的致死率均为100%,显示出良好的杀虫活性.     

新型6-(4-氨基苯基)-4,5-二氢-3(2H)-哒嗪酮α-氨基膦酸酯衍生物的合成

以乙酰苯胺与丁二酸酐为原料,经Friedel-Crafts酰化反应、水解脱乙酰基和水合肼缩合制得中间体6-(4-氨基苯基)-4,5-二氢-3(2H)-哒嗪酮(3);3与芳醛和亚磷酸二乙酯经类Mannich-type反应合成了5个新型的6-(4-氨基苯基)-4,5-二氢-3(2H)-哒嗪酮α-氨基膦酸酯衍生物,其结构经1H NMR,~(13)C NMR,31P NMR,IR和ESI-MS表征。     

4-氟-1,2-二氢-3,6-哒嗪二酮及其衍生物的合成

本文报导了4-氟-1,2-二氢-3,6-哒嗪二酮(Ⅱ)及其衍生物3,6-二氯-4-氟哒嗪(Ⅲ)、3-甲氧基-4-氟-6-氯哒嗪(Ⅳ)、3-邻甲苯氧基-4-氟-6-氯哒嗪(Ⅵ)、1-苯基-3-羟基-4-氟-6-哒嗪酮(Ⅶ)等五种新化合物的合成,探讨了(Ⅲ)同亲核试剂的反应性能和部分化合物的药理实验结果.     

Synthesis of Methyl 5(6)-(4-Aminophenoxy)- and 5(6)-(2-Aminophenoxy)-2-benzimidazolyl Carbamates and Their Biological Properties

A procedure was developed for preparation of methyl 5(6)-(4-aminophenoxy)- and 5(6)-(2-aminophenoxy)-2-benzimidazolyl carbamates by reaction of 3,4,4`-triaminodiphenyl or 3,4,2`-triaminodiphenyl ethers respectively with methyl cyanocarbamate in water solution in the presence of 7-10 molar excess of acetic acid. The helminthicidal properties, embryotoxicity, and overall toxicity of compounds obtained were estimated.     

2-Polyfluoroalkylchromones. 14. Synthesis of 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles

3-Chloro-2-polyfluoroalkyl- and 3-chloro-6-nitro-2-polyfluoroalkylchromones were synthesized. These compounds react with N₂H₄·2HCl on boiling in ethanol to form 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles.     

Novel benzamides as selective and potent gastrokinetic agents. III. Synthesis and structure-activity relationships of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]-benzamides.

A series of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]benzamides (11-64) were prepared and evaluated for gastrokinetic activity by determining their effects on the gastric emptying of phenol red semisolid meal in rats. The N-4 substituent includes alkyl, phenoxyalkyl, (4-fluorobenzoyl)alkyl, and heteroarylmethyl groups. The benzamide derivatives, having an isopropyl, isoamyl, neopentyl, 3-(4-chlorophenoxy)-propyl, or pyridylmethyl group at N-4, showed potent in vivo gastric emptying activity. In particular, 4-amino-5-chloro-2-ethoxy-N-[[4-(3-pyridylmethyl)-2- morpholinyl]methyl]benzamide (57b) was equipotent to the 4-fluorobenzyl analogue 1b (AS-4370 as its citrate) in the gastrokinetic activity on phenol red semisolid meal in rats and mice, and on resin pellet solid meal in rats. Moreover, compound 57b was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests. Structure-activity relationships of compounds with various substituents at N-4 are also discussed.     

5-取代氨基-12-取代苯并[c]菲啶衍生物的合成、晶体结构及生物活性

为了寻找新的高活性农药, 利用2-甲基苯甲腈与不同的醛反应, 再通过2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ)脱氢或NaH和CH3I氮甲基化, 合成了3个系列共18个5-取代氨基-12-取代苯并[c]菲啶衍生物, 其中15个是未见文献报道的化合物. 它们的结构均经1H NMR, 13C NMR, IR和高分辨质谱表征; 用X射线衍射测定了化合物5-氨基-12-(4-二乙氨基苯基)-11,12-2H-苯并[c]菲啶盐酸盐(3c)的晶体结构. 初步的生物活性测试结果表明, 部分化合物具有一定的杀菌活性和促进黄瓜子叶生根活性.     

N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类新化合物的合成及生物活性

以N-吡啶基吡唑甲酸和2-氨基-3-甲基苯甲酸为起始原料,经由亲核加成、环化和酰化等多步反应合成了一系列结构新颖的N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类化合物.测试了所合成化合物的杀虫及抑菌活性,结果表明,新化合物大多化合物在200 mg·L^-1浓度下对东方粘虫(Mythimna separataWalker)具有一定的杀虫活性,尤其是N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)乙酰胺(8a)和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3-氯-2,2-二甲基丙酰胺(8e)致死率可达70%;部分化合物在50 mg·L^-1浓度下对油菜菌核病菌的抑菌活性相对较好(54.5%~63.6%),优于triadimefon和chlorantraniliprole;部分化合物如N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3,3-二甲基丁酰胺80和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-4-氟苯甲酰胺(8h)对苹果轮纹病菌具有中等抑菌活性.值得注意的是,化合物8e的杀粘虫活性和对油菜菌核病菌的抑菌活性都较为突出,可用作新农药创制研究的新型参考结构.     

Synthesis,characterization and antibacterial activity of 1-([6-bromo-2-hydroxy-naphthalen-1-yl]arylphenyl)methyl)-3-chloro-4-(arylphenyl)-azetidin-2-one

One-pot synthesis of 1-([6-bromo-2-hydroxy-naphthalen-1-yl]-aryl-phenyl)methyl)-3-chloro-4-(aryl-phenyl)azetidin-2-ones has been reported in the present research work via Staudinger [2 + 2] ketene-imine cycloaddition reaction pathway. The reaction of 1-((Benzylideneamino)(aryl)methyl)-6-bromo-naphthalen-2-ols with chloroacetic acid and triethylamine afforded 1-([6-bromo-2-hydroxynaphthalen-1-yl]aryl-phenyl)methyl)-3-chloro-4-(aryl-phenyl)azetidin-2-ones. For the structural elucidation of series of compounds, different analytical and spectroscopic techniques such as elemental analysis, IR spectra, ¹H-NMR spectra and mass spectra were used. All the newly synthesized compounds were tested for their anti-bacterial activity studies. It revealed that some of the compounds possesses moderate to good activities as compared to standard drugs. The widest spectrum of anti-bacterial activities against both gram-positive and gram-negative bacterial strains among the examined compounds possessed having more hydroxyl group along with β-lactam ring compared to other substituted azetidinones.     

A facile synthesis of 3-substituted 2-cyanoquinazolin-4(3H)-ones and 3-alkyl-2-cyanothieno[3,2-d]pyrimidin-4(3H)-ones via 1,2,3-dithiazoles

The reaction of methyl anthranilate with 4,5-dichloro-1,2,3-dithiazolium chloride (Appel's salt) in the presence of pyridine (2 equivalents) in dichloromethane at room temperature gave methyl N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)anthranilate ( 3a ) (50% yield), which reacted with sterically less hindered primary alkylamines to give directly 3-alkyl-2-cyanoquinazolin-4(3H)-ones 5 in moderate to good yields. With tert-butylamine, N-(2-methoxycarbonylphenyl)iminocyanomethyl N-(tert-butyl) disulfide 7 and methyl 2-(N-cyanothioformamido)anthranilate ( 8 ) were isolated in 33% and 59% yields, respectively. The cyano group of quinazoline 5a (R = CH₃) is readily displaced by various nucleophiles to give 2-substituted quinazolinones 11–19 , which indicates that compounds 5 can be utilized as starting materials for the synthesis of new 2-substituted quinazolines. Similarly 3-alkyl-2-cyanomieno[3,2,-d]pyrimidin-4(3H)-ones 22 were prepared from methyl 3-[N-(4-chloro-5H-1,2,3-dimiazol-5-ylidene)]-2-thiophencarboxylate ( 21 ) in moderate to good yields.     

Synthesis and characterization of new α,β‐unsaturated γ‐lactones: Alkyl 3‐acetyl‐4‐hydroxy‐2‐methyl‐5‐oxo‐2,5‐dihydrofuran‐2‐ylcarbamates

A convenient procedure for the preparation of carbamate derivatives of 5‐oxo‐2,5‐dihydrofuran ( 3 ) was described. The method is based on the Michael type addition of three alkyl carbamates ( 2 ) with 4‐acetyl‐5‐methyl‐2,3‐dihydro‐2,3‐furandione ( 1 ). According to ¹H nmr spectra of compounds show tautomeric forms ( 3,4,5 ) in CDC1₃. In the solid state the synthesized compounds are enol forms ( 3 ). The products were characterized with molecular spectroscopic methods.     

The unprecedented preparation of dinuclear zinc(II) complexes from 4-halido-2-[(3-cyclohexylaminopropylimino)methyl]phenol

Three new centrosymmetric trinuclear nickel(II) and manganese(II) complexes, Ni[Ni(CH(3)COO)(CPA)](2) (1), Ni[Ni(CH(3)COO)(BPA)](2) (2), Mn[Mn(CH(3)COO)(BPA)](2) (3), where H(2)CPA = N,N'-bis(5-chlorosalicylidene)-1,3-propanediamine, H(2)BPA = N,N'-bis(5-bromosalicylidene)-1,3-propanediamine, and two new centrosymmetric dinuclear zinc(II) complexes, [Zn(2)(CMP)(2)] (4) and [Zn(2)(BMP)(2)] (5), where H(2)CMP = 4-chloro-2-{[3-(5-chloro-2-hydroxybenzyl)aminopropylimino]methyl}phenol, and H(2)BMP = 4-bromo-2-{[3-(5-bromo-2-hydroxybenzyl)aminopropylimino]methyl}phenol, have been prepared from the Schiff bases derived from 5-halido-substituted salicylaldehydes with N-hexylpropane-1,3-diamine under solvothermal conditions. The complexes have been characterised by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction studies. The complexes 1, 2, and 3 crystallise in the monoclinic space group P2(1)/c with cell dimensions a = 9.347(1), b = 11.507(2), c = 18.539(2) ?, β = 93.774(2)°, Z = 2 (for 1), a = 9.111(4), b = 12.089(6), c = 18.724(8) ?, β = 92.117(7)°, Z = 2 (for 2), and a = 11.328(2), b = 22.468(5), c = 8.270(2) ?, β = 93.74(3)°, Z = 2 (for 3), while complexes 4 and 5 crystallise in the triclinic space group P1, with cell dimensions a = 7.483(1), b = 9.990(2), c = 12.155(2) ?, α = 75.27(3), β = 85.00(3), γ = 73.82(3)°, Z = 1 (for 4), and a = 7.008(1), b = 10.081(2), c = 13.095(3) ?, α = 100.62(3), β = 95.51(3), γ = 104.03(3)°, Z = 1 (for 5). It is interesting that the mono-Schiff bases 4-chloro-2-[(3-cyclohexylaminopropylimino)methyl]phenol (HCCP) and 4-bromo-2-[(3-cyclohexylaminopropylimino)methyl]phenol (HBCP) used to prepare the nickel(II) and manganese(II) complexes were transferred to bis-Schiff bases H(2)CPA and H(2)BPA in the complexes 1, 2, and 3, while the mono-Schiff bases HCCP and HBCP used to prepare the zinc(II) complexes were transferred to novel ligands H(2)CMP and H(2)BMP, bearing the unexpected, newly formed carbon-nitrogen single bond.     

(Z)-2-苯氧(硫)基甲基-2-戊烯-γ-内酯和(Z)-2-苯氧(硫)亚甲基-γ-戊内酯的简便合成

以3-苯氧(硫)基丙炔(1)为原料,经5步反应合成(Z)-2-苯氧(硫)基甲基-2-戊烯-γ-内酯(8)和(Z)-2-苯硫亚甲基-γ-戊内酯(9).合成关键步骤为TMSCl/NaI/H2O/CH3CN体系中化合物(3)的碘氢化和去共轭.