新型茼蒿素类似物的合成和抗虫构效关系研究

Twenty-one tonghaosu analogs were synthesized via hydroamination or selective reduction of the endocyclic double bond of the corresponding dienol spiroketals. Structures of all the new compounds were confirmed by ^1H NMR, IR, MS, HREIMS or elemental analysis. Their antifeedant activity against large white butterfly （Pieris brassicae L） and larvicidal activity toward mosquito （Culex quinquefasciatus Say） were examined. Some of them exhibited antifeeding activities comparable to or stronger than tonghaosu Z-1. Based on the activity data, the preliminary structure-activity relationship was also discussed, which might be instructive for finding out lead compounds with better bioactivities in the future.     

Synthesis and Bioactivity of Novel N,N′‐Diacylhydrazine Derivatives Containing Furan (III)

42 novel diacylhydrazine derivatives containing furan were synthesized by the reaction of 5‐substituted phenyl‐2‐furoyl chloride with substituted benzohydrazide in anhydrous dichloromethane under reflux. Their structures were confirmed by IR, ¹H NMR, MS and elemental analysis. Insecticidal and antitumor activity of these new compounds was evaluated. The preliminary bioassays showed that the target compounds exhibited larvicidal activity to the Mythimna separate, some of them exhibited good or moderate larvicidal activity. At the concentration of 0.1%, compounds I2 , I4 , I5 , and III1 showed 95.0%, 90.0%, 95.0% and 95.0% larvicidal activity to Mythimna separate respectively. Some compounds such as I2 , I4 , I5 and III1 showed the typical IGRs' activity, which could induce the larvae premature, abnormal, and lethal larval molt. Results of anticancer activity indicated that some compounds exhibited potential activity against some human cancer cell lines, for example, I1 and IV showed good activity to the BGC‐823 and the inhibitory rates were 60.86% and 61.94% respectively at 10 µmol/L.     

Synthesis,Biological Activity of Pyrimidine Linked with Morpholinophenyl Derivatives

A new series of 5‐fluoro‐N⁴‐(3‐(4‐substitutedbenzylamino)phenyl)‐N²‐(4‐morpholinophenyl)pyrimidine‐2,4‐diamine derivatives ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j ) are prepared from using an intermediate compound 5‐fluoro‐N⁴‐(3‐(aminophenyl)‐N²‐(4‐morpholinophenyl)pyrimidine‐2,4‐diamine ( 5 ). The structures of the newly synthesized products are established from their spectral ¹H‐NMR, ¹³C‐NMR, ¹⁹F‐NMR, ESI‐MS, and analytical data. Here we report the synthesized compounds and larvicidal activity. All the compounds are screened for their significant larvicidal activity against third instar larvae at 24, 48, and 78‐h time exposure, and values were compared with standard drug Malathion. The Compounds 7i , 7a , 7c , 7f , and 7j exhibited significant activity. However the compounds 7b , 7e , 7d , and 7h showed excellent activity when compared to the above compounds and to standard drug malathion too because of the presence of mild electron withdrawing groups such as trifluoro, fluorine, hydroxy, nitro, and methoxy derivatives which are attached to the benzyl ring.     

Comparison of 1‐Ethyl‐5H‐tetrazole and 1‐Azidoethyl‐5H‐tetrazole as Ligands in Energetic Transition Metal Complexes

Energetic coordination compounds (ECC) based on 3d or 4d transition metals show promising characteristics to be used as potential replacements for highly toxic lead‐containing primary explosives. Herein we report the synthesis of 12 new ECC based on 1‐azidoethyl‐5H‐tetrazole (AET) or 1‐ethyl‐5H‐tetrazole (1‐ETZ) as nitrogen‐rich ligands as well as various central metals (Cu²⁺, Fe²⁺, Zn²⁺, Ag⁺) and anions such as perchlorate and nitrate. The influence of the increased endothermicity by adding an additional azide group was studied by comparing analogous ECC based on AET and 1‐ETZ. Furthermore, the compounds were extensively analyzed by XRD, IR, EA, solid‐state UV/Vis, and DTA as well as their sensitivities toward impact and friction were determined with BAM standard techniques, together with their sensitivity against electrostatic discharge. The sensitivities were compared with the one toward ball drop impact measurements. Classical initiation tests (nitropenta filled detonators) and ignition by laser irradiation highly prove the potential use of the most promising compounds in lead‐free initiation systems.     

Heterocyclic synthesis via enaminones: Novel synthesis of (1H)‐pyridin‐2‐one,pyrazolo[1,5‐a]pyrimidine and isoxazole derivatives incorporating a N‐methylphthalimide and their biological evaluation

Novel synthesis of (1H)‐pyridin‐2‐one, pyrazolo[1,5‐a]pyrimidine and isoxazole derivatives incorporating N‐methylphthalimide moiety are reported. Reaction of enaminone 2 with malononitrile affords 4. Condensation of 2 with cyanothioacetamide or benzoylacetonitrile affords compounds 6 and 7 respectively. Reaction of 2 with hydrazine hydrate afford 2,3‐dihydrophthalazine‐1,4‐dione ( 10 ). Condensation of 2 with hydroxylamine and 3‐aminopyrazole derivatives affords compounds 12 and 15a,b respectively. Antimicrobial and antifungal activity were determined for representative compounds and most of them showed moderate activity as antimicrobial agents, while compounds 2 and 7 show strong activity against Aspergillus niger. The structure of the newly synthesized compounds was elucidated by elemental analyses and ¹H nmr spectra and some cases by ¹³C nmr investigation.     

Synthesis and Insecticidal Evaluation of Novel Anthranilic Diamides Derivatives Containing 4‐Chlorine Substituted N‐Pyridylpyrazole

To search for potent insecticides targeting at ryanodine receptors (RyRs), a series of novel anthranilic diamides analogs containing 4‐chlorine N‐pyridylpyrazole were designed and synthesized. Their insecticidal activities were evaluated and the preliminary structure‐activity relationships (SARs) were discussed. The insecticidal results showed that some of the compounds (8a—8h, 8m, 8n) exhibited good larvicidal activities against oriental armyworm at 2.5 mg·L^–1, and compound 8m possessed 60% insecticidal activity at 0.5 mg·L^–1. For diamondback moth, 8m exhibited better activity than Chlorantraniliprole at a hundred fold preference. The calcium imaging technique experiment results suggested that compound 8m could increase the intracellular [Ca²⁺]_i. With the neurons preincubated experiment, the results confirmed that the target of this series of compounds could be RyRs in the central larvae neurons of oriental armyworm. The results indicated that compound 8m could respond as a potential modulator of the insect ryanodine receptor.     

A new approach to the synthesis of 2‐aryl‐substituted benzimidazoles,quinazolines, and other related compounds and their antibacterial activity

A new synthesis method of benzimidazoles, dihydroquinazolines, and other related compounds containing a 2,4‐dihydroxyphenyl moiety was elaborated. Their structures were identified from elemental, infrared, ¹H NMR, ¹³C NMR, and mass spectra analyses. The minimal inhibitory concentration values of the compounds toward eight reference bacterial strains were determined by the two‐fold serial microdilution broth method. The compounds exhibited substantial inhibitory effects against the Gram‐positive strains tested contrary to Gram‐negative ones. The compounds of imidazopyridine, N‐methylbenzimidazole, and dihydroquinazoline structures exhibited the largest activity. The magnification of covering a two‐nitrogen atom heterocyclic ring fused to a benzene one decreases the biological effect. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:265–275, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21012     

茼蒿素类似物的合成

本文报道了天然昆虫拒食剂茼蒿素的一些新类似物的合成。整个工作以取代的呋喃丙醇为前体, 经间氯过氧苯甲酸氧化、Luche还原、双键环氧化、酸催化的螺环缩酮化以及自由基媒介的脱水反应给出目标产物。     

Design,Synthesis, and Insecticidal Activity of 1,5‐Diphenyl‐1‐pentanone Analogues

Three series of novel 1,5‐diphenyl‐1‐pentanone derivatives were designed and synthesized. Their structures were characterized by IR, ¹H NMR techniques, and elemental analysis. The insecticidal activities of the new compounds were preliminarily evaluated. The bioassay results indicated that the compounds X11 – X30 displayed better aphicidal activity against Aphis gossypii than compounds X1 – X10 and the lead compound (E)‐1,5‐diphenyl‐1‐penten‐1‐one ( A ). The inhibitory rates of compounds X6 and X29 were 100% against Plutella xylostella (L.) at 600 mg·L^?1. Compounds X12 , X13, X19 , X24, X25 , X26 and X27 showed higher insecticidal activity against Tetranychus cinnabarinus (Boisduval) at 600 mg·L^?1 than the lead compound ( A ).     

Synthesis and Characterization of Novel Phthalimide‐pyrano[3,2‐c]chromene and Phthalimide‐pyrano‐2‐one Hybrids

Coumarin skelton holds substantial promise for further exploration because of its immense pharmacological potential. In this pursuit, a series of phthalimide‐chromen and phthalimide‐pyran‐2‐one hybrids were synthesized in efficient yields via one‐pot multicomponent reaction of aldehyde linked to phthalimide moiety, 4‐hydroxy coumarin/4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one, and malanonitrile by Knoevenagel reaction at room temperature in the presence of DABCO as catalyst. The compounds were characterized by ¹H NMR and ¹³C NMR, MS, and FTIR. All the compounds consisting of phthalimide‐chromen/pyrano‐2‐one moieties tethered by spacers of varying lengths were evaluated for their biological activity in Ellman's assay. Most of the compounds feebly inhibited Acetylcholinesterase Enzyme and were inactive toward Butyrylcholinesterase Enzyme.     

Synthesis and Antimicrobial Evaluation of Some Novel 5‐Phenyl‐5H‐thiazolo[4,3‐b][1,3,4]thiadiazole Systems

Condensation of 2‐amino‐5‐phenyl‐5H‐thiazolo[4,3‐b] [1,3,4] thiadiazoles ( 1 ) with some carboxylic acid derivatives furnished corresponding compounds 2–4 , respectively. Alkylation of 1 with benzoylchloride and 4‐chlorobenzyl chloride afforded thiazolo[4,3‐b][1,3,4]thiadiazole derivatives 5 and 6 , respectively. Similarly, transformation of 1 with chloroacetyl chloride yielded chloroacetamide derivative 7 . The later compound was subjected to react with potassium thiocyanate or piperazine whereby, the binary thiazolidinone derivative 8 and N ¹ ,N⁴‐disubstituted piperazine 9 were produced, respectively. Also, the reactivity of 1 toward various active methylene reagents was investigated. Accordingly, our attempts to synthesize the tricyclic heterocyclic system 10 , 11′ , 12 ^′ by reaction of 1 with chloroacetonitrile, 4‐oxo‐4‐phenylbutanoic acid and/or diethylmalonate in presence of acetyl chloride was furnished 10 , 11 , and 12 . The newly synthesized compounds were screened as antimicrobial agent.     

Synthesis,Spectral Characterization and Antioxidant Activity of Novel Zafirlukast Sulfonyl Derivatives

A new series of cyclopentyl 3‐(2‐methoxy‐4‐(piperazine‐1‐carbonyl)benzyl)‐1‐methyl‐1H‐indol‐5‐ylcarbamate sulfonyl derivatives were synthesized by the reaclion of 4‐((5‐(cyclopentyloxycarbonylamino)‐1‐methyl‐1H‐indol‐3‐yl)methyl)‐3‐methoxybenzoic acid (ZAK drug intermediate) with Boc piperazine in the presence of EDC?HCl, HOBt, TEA in DMF followed by deboxylation by using 2N HCl or 35 % HCl in acetone to get an intermediate compound. Further, this compound was treated with various substituted benzene sulfonyl chlorides in the presence of TEA in THF to afford title compounds. All the title compounds were characterized by ¹HNMR, ¹³CNMR, IR and mass spectral data. The title compounds and starting material were evaluated for their antioxidant activity by using the DPPH, H₂O₂ and NO methods. The results revealed that some of the compounds have shown significant antioxidant activity.     

Novel 1,3,4‐Oxadiazole Derivatives of Dihydropyrimidinones: Synthesis,Anti‐Inflammatory,Anthelmintic, and Antibacterial Activity Evaluation

The present study depicts synthesis of a series of some novel 5‐(5‐(aryl)‐1,3,4‐oxadiazol‐2‐yl)‐3,4‐dihydro‐6‐methyl‐4‐styrylpyrimidin‐2(1H)‐one derivatives. All the newly synthesized compounds were characterized by FTIR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The compounds were evaluated for their in vivo anti‐inflammatory activity by the carrageenan‐induced rat paw edema method. The compounds were also screened for their anthelmintic activity on Indian earthworms and antibacterial activity against some gram positive and gram negative strains of bacteria. This pharmacological activity evaluation revealed that, among all the compounds screened, compounds 4b and 4c were found to have promising anti‐inflammatory activity. Interestingly, compounds 4b , 4c , and 4i exhibited appreciable anthelmintic property, while compounds 4c , 4g , and 4h showed leading antibacterial activity against the selected pathogenic strains of bacteria.     

Synthesis and antimicrobial activity of 2‐substituted‐2,3‐dihydro‐5‐propoxy‐1H‐1,3,2‐benzodiazaphosphole 2‐Oxides

Several 2‐alkylcarbamato/thiocarbamato/aryloxy/trichloromethyl‐2,3‐dihydro‐5‐propoxy‐1H‐1,3,2‐benzodiazaphosphole 2‐oxides ( 4 and 6 ) were synthesised by reacting 4‐propoxy‐o‐phenylenediamine ( 1 ) with various N‐dichlorophosphinyl carbamates ( 3 ), aryl phosphorodichloridates ( 5a‐f ) and trichloromethyl phosphonic dichloride ( 5g ) in the presence of triethylamine at 45‐65 °C. Their ir, ¹H, ¹³C, ³¹P nmr and mass spectral data are discussed. The compounds were screened for antifungal activity against Curvularia lunata and Aspergillus niger and for antibacterial activity against Bacillus subtilis and Escherichia coli. Most of these compounds exhibited moderate activity in the assays.     

Synthesis and Antimicrobial Activity of 1‐[(Substituted Carbamoyl)Amino]‐1H,3H‐1λ5‐[1,3,2]oxazaphospholo[3,4‐a]benzimidazol‐1‐ones

1‐[(Substituted carbamoyl)amino]‐1H,3H‐1λ⁵‐[1,3,2]oxazaphospholo[3,4‐a]benzimidazol‐1‐ones were synthesized by reacting benzimidazole 2‐methanol (4) with different chlorides of carbamidophosphoric acids (3) in the presence of triethylamine at 40–45°C. Their ¹H, ¹³C, and ³¹P NMR spectral data were discussed. The title compounds were tested for their activity against the fungi Aspergillus niger and Fusarium solani and bacteria Staphylococcus aureus and Escherichia coli. These compounds showed moderate antibacterial activity when compared with antifungal activity.     

Antimicrobial Evaluation of New Quinoxaline Derivatives Synthesized by Selective Coupling with Alkyl Halides and Amino Acids Esters

Alkylation of quinoxaline scaffold 1 in the presence of K₂CO₃ preferred N‐alkylation than O‐alkylation. Quinoxaline hydrazide 6 was successfully coupled with various amino acids, esters, and amines via azide‐coupling method. New heterocyclic compounds containing quinoxaline linked to 1,3,4‐oxadiazolethione or pyrazole were obtained from cyclization of 6 with CS₂ and acetylacetone, respectively. A series of hydrazide Schiff's bases were formed from hydrazide 6 by condensation with a set of aldehydes and ketones. NMR spectroscopy and mass spectrometry were used for structure elucidation of new compounds. The antimicrobial activity of the synthesized compounds was investigated toward two wild‐type bacterial strains (Staphylococcus aureus and Escherichia coli ) and two fungal species (Alternaria brassicicola and Fusarium oxysporum ). Four compounds displayed a significant activity toward S. aureus . The ester 4 showed higher activity than the standard drugs, which make it a promising lead compound.     

Synthesis,Tautomerism, and Antiradical Activity of Novel Pteridinetrione Derivatives

Synthesis of 1‐methyl‐6‐((2‐(aryl‐(heteryl‐))‐2‐oxoethyl) pteridine‐2,4,7(1H,3H,8H)‐triones via [4 + 2]‐cycloaddition of 1‐methyl‐5,6‐diaminouracil with ethyl 4‐aryl(heteryl)‐2,4‐dioxobutanoates is described in presented work. It was established that the reaction occurs regioselectively and proceeds under refluxing of starting compounds in acetic acid for 60 min. The structures of synthesized compounds were proven by complex of physicochemical methods including infrared, ¹H‐, ¹³C‐NMR spectroscopy, liquid chromatography–mass spectrometry, and electron impact–mass spectrometry. Based on the detail analysis of the correlational NMR spectral data (correlation spectroscopy, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, and Nuclear Overhauser effect spectroscopy), it was determined that in dimethyl sulfoxide solution, the 1‐methyl‐6‐((2‐(aryl‐(heteryl‐))‐2‐oxoethyl)pteridine‐2,4,7(1H,3H,8H)‐triones exist in two tautomeric forms: ketone (A) and enol (B). It was also found that tautomeric behavior of aforementioned compounds in hexadeuterated dimethyl sulfoxide is sensitive to the nature of the aryl or heteryl substituent at the position 6 of ring. The electron donating groups shift equilibrium to the tautomer A, while electron withdrawing – to the tautomer B. The synthesized compounds were tested on antiradical activity. It was found that obtained compounds reveal radical scavenging activity comparable or higher than ascorbic acid.     

Synthesis and Antimicrobial Evaluation of Novel Derivatives of Semicarbazide and 1,2,4‐triazole

Reaction of phenoxyacetic acid hydrazide with isocyanate was used to the synthesis of new semicarbazide derivatives. Cyclization of these compounds in a 2% aqueous solution of sodium hydroxide led to formation of 1,2,4‐triazole‐3‐one. The chemical structure of synthesized compounds was confirmed by elemental analysis and spectroscopic methods (¹H and ¹³C NMR). On the basis of the NMR, spectra were found that cyclic compounds 1,2,4‐triazole exist in the ‐one form. Moreover, all derivatives were examined for their in vitro activity against some species of bacteria. New compounds presented mild or moderate antimicrobial activity only against reference Gram‐positive bacteria. Two derivatives (one semicarbazide and one triazole) showed bactericidal or bacteriostatic activity.     

Synthesis and Antimicrobial Evaluation of Novel Polyfused Heterocycles‐Based Quinolone

Syntheses of some new heterocyclic compounds incorporating quinolone moieties were achieved via reaction of 4‐hydroxy‐7‐methoxyquinolin‐2(1H)‐one ( 1 ) or 3‐bromo‐4‐hydroxy‐7‐methoxyquinolin‐2(1H)‐one ( 2 ) with binucleophilic reagents. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H‐NMR and mass spectra). The newly synthesized compounds were screened for their antibacterial activity against Gram‐positive bacteria (Bacillus thuringiensis) and Gram‐negative bacteria (Escherichia coli). The results showed clearly that compounds 1 and 3 are the more potent antibacterial agents against E. coli, compounds 4 , 5 , 6 and 8 , 9 , 10 , 11 , 12 , 13 exhibited moderate activities against E. coli strain, and compounds 7 and 11 exhibited weak activities compared with Gentamicin as a well known standard drug.     

Reactions of Peroxynitrite with Phenolic and Carbonyl Compounds: Flavonoids are not Scavengers of Peroxynitrite

Peroxynitrite (ONOO⁻, oxoperoxonitrate(1−)), an isomer of nitrate that oxidizes and nitrates biomolecules, is likely to be formed in vivo from the reaction of superoxide with nitrogen monoxide. To determine whether flavonoids scavenge peroxynitrite as postulated in the literature, we studied the reactions of peroxynitrite with phenol, hydroquinone, catechol, and the flavonoid monoHER. These reactions are first‐order with respect to peroxynitrous acid and zero‐order with respect to the organic compounds, and proceed as fast as the isomerization of peroxynitrous acid to nitrate. In vivo, a large fraction of all peroxynitrite is likely to react with carbon dioxide to form an unstable adduct, the 1‐carboxylato‐2‐nitrosodioxidane anion (ONOOCO). The presence of phenolic compounds did not influence the rate of disappearance of this adduct, which was ca. 4×10² s⁻¹. On the basis of these kinetic studies, it can be concluded that flavonoids are not scavengers of peroxynitrite. The products from the reaction of peroxynitrite with hydroquinone (benzene‐1,4‐diol) and catechol (benzene‐1,2‐diol) are para‐benzoquinone and ortho‐benzoquinone, respectively; no nitrated products were found. In a subsequent reaction, ortho‐quinone reacted with nitrite, a common contaminant of peroxynitrite preparations to form 1,2‐dihydroxy‐4‐nitrobenzene. We also investigated whether carbonyl compounds could redirect the reactivity of peroxynitrite toward nitration, as carbon dioxide does. The reaction with acetone is first‐order with respect to peroxynitrite and first‐order with respect to the carbonyl compound. The rate constant is 1.8 M ⁻¹s⁻¹ at neutral pH and 20°; peroxynitrite does not react with the carbonyl compounds dimethyl acetamide, L ‐alanylalanine, or methyl acetate. It is not likely that the carbonyl compounds or the mono‐, di‐, or polyphenolic compounds can scavenge peroxynitrite in vivo.