Synthesis,characterization, and investigations of antimicrobial activity of 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4(5H)-dione

Chalcone-like compounds 3a–l, 2-(benzylidene)-3,4-dihydronaphthalen-1(2H)-one, were synthesized from the addition of different benzaldehyde derivatives (2a–l) to 1,2,3,4-tetrahydro-1-napthalone (1) in basic medium. Mn(OAc)₃-mediated addition of dimedone (4) to chalcone-like compounds gave the spirobenzofuran derivatives (5a-l), 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4 (5H)-dione, in good yields. The structures of synthesized compounds 5a–l were elucidated on basis of spectral data (NMR, IR) and elemental analysis. In addition, their antibacterial activities were screened against some human pathogenic microorganisms.     

Synthesis of some novel 5-substituted benzamido-6-arylamino-pyrazolo[3,4-D]pyrimidin-4-one derivatives for herbicidal activity

Abstract

Sixteen novel 3-methylthio-5-substituted benzamido-6-arylamino-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H)-one derivatives (4a–p) were successfully synthesized from iminophosphoranes, aryl isocyanate, and substituted benzoylhydrazine. The structures of the title compounds were elucidated by FT-IR, ¹H NMR, ¹³C NMR, and HRMS. Herbicidal activity of the compounds 4a–p against Brassica napus (rape), Echinochloa crusgalli (barnyard grass), Cucumis sativus (cucumber), and Triticum aestivum (wheat) were determined. The results showed that 5-(2-chlorobenzamido)-6-phenylamino-3-methylthio-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H)-one (4c) displayed remarkable inhibition activity against the stalk and root of rape with 100% inhibition rate at the dosages of 10?mg/L and 100?mg/L, and 5-(4-nitrobenzamido)-6-phenylamino-3-methylthio-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H) -one (4d) exhibited excellent activity against the stalk and root of barnyard grass with 100% inhibition rate at the same dosages.     

Phenolic compounds from the aqueous extract of Acacia catechu

From the aqueous extract of Acacia catechu,two new phenolic compounds(3R,4R)-3-(3,4-dihydroxyphenyl)-4-hydroxycy-clohexanone (1) and(4R)-5-(1-(3,4-dihydrophenyl)-3-oxobutyl)-dihydrofuran-2(3H)-one(2) were obtained.Their structures were determined on the basis of spectroscopic analysis.Free-radical scavenging activities of them were evaluated.     

Concise Synthesis of Ring-Fission Metabolites of Epicatechin: 5-(3,4-Dihydroxybenzyl)dihydrofuran-2(3H)-one M6

The ring-fission metabolites of epicatechin, 5-(3,4-dihydroxybenzyl)dihydrofuran-2(3H)-one M6 and 3-methylated M6, were prepared from 3,4-dihydroxybenzaldehyde and furan-2(5H)-one using two new concise methods in excellent yields (three or two steps in 40–60% overall yield).     

取代吡唑-5-酰基杂环衍生物的合成、结构与生物活性

为了寻求新的含吡唑双杂环先导化合物. 用4-取代-1-甲基-3-乙基-5-吡唑甲酰氯与2-噻唑烷酮、2-噻唑硫酮、2-噁唑烷酮等含氮杂环反应得到了12个含吡唑环的双杂环化合物. 化合物结构用IR, ¹H NMR, MS和元素分析进行了表征. 并用X射线单晶衍射法测定了化合物3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噁唑烷-2-酮(3k)的晶体结构. 晶体为单斜晶系, P2₁/n (#14)空间群, a＝1.52175(3) nm, b＝0.52970(1) nm, c＝1.58185(3) nm, β＝104.893(4), V＝1.2323(4) nm³, Z＝4, D_c＝1.45 g/cm³, F(000)＝560.00, R₁＝0.064, wR₂＝0.193. 初步生物活性实验结果表明, 在25 mg/L浓度下, 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-酮(3c), 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-硫酮(3g)对水稻稻瘟病菌(Pyricularia oryzae)的抑制活性达到40%. 在500 mg/L浓度下, 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噻唑烷-2-酮(3d), 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噁唑烷-2-酮(3l)对稻黑尾叶蝉(Nephotettix cinc-ticeps)的抑制活性达到53.37%.     

Directed regiospecificity of 1,3-dipolar cycloaddition of 2-diazopropane to 4- and 5-substituted pyridazin-3(2H)-ones

6-Methoxy-2-methylpyridazin-3(2H)-one ( 1 ) gave with 2-diazopropane ( 8 ) a mixture of 3H-pyrazolo[3,4-d]-pyridazin-4(5H)-one derivative 12 , as the main product, and -7(6H)-one derivative 10 , as the minor product. On the other hand, 4-substituted pyridazin-3(2H)-ones 2, 3 , and 4 gave 3H-pyrazolo[3,4-d]pyridazin-7(6H)-one 10 , exclusively, while 5-substituted pyridazin-3(2H)-ones 5, 6 , and 7 produced only the isomeric 3H-pyrazolo[3,4-H]pyridazin-4(5H)-one 12 . The 5-phenylsulfonyl derivative 13 gave with 8 by elimination of a molecule of nitrogen, followed by rearrangement, 1,2-diazepine derivative 15 and with an excess of 8 3H-pyrazolo[3,4-d][1,2]diazepine derivative 16. 1 ,2-Dimethylpyridazine-3,6-(1H,2H)-dione and its derivatives 18 and 19 produced 3H-pyrazolo[3,4-d]pyridazine-4,7(5H,6H)-dione derivative 23 , while from 17 and 1-diazoindane ( 24 ) the spiro compound 27 was obtained. The 1,2-dihydro and 3a,7a-dihydro intermediates 21 and 25 were isolated.     

Imines and lactones derived from friedelanes and their cytotoxic activity

Abstract

Friedelan-3-one (1) and friedelane-3,16-dione (2) isolated from leaves and branches of Maytenus robusta Reissek were subjected to structural modifications via nucleophilic addition to the carbonyl group and Baeyer-Villiger oxidation in order to synthesize potential cytotoxic compounds. The oximes friedelane-3-hydroxyimino (3) and 3-hydroxyiminofriedelan-16-one (4) together with the lactones friedelane-3,4-lactone (5) and 3,4-lactonefriedelan-16-one (6) were characterized by IR and NMR spectroscopic analyses. Compounds 4 and 6 are reported for the first time. Cytotoxic screening via MTT assay in human leukemia cell lines (THP-1 and K562) demonstrated no significant improvement of compounds 3-6 when compared to the starting materials. Only compounds 3 and 5 demonstrated an improvement against K562 cells. However, the same assay on ovarian and breast cancer cell lines (TOV-21G and MDA-MB-231) showed a reduction in the IC₅₀ for compounds 4-6, indicating that ring A modifications may enhance the biological potential.     

Antimicrobial and antiquorum-sensing activity of Ricinus communis extracts and ricinine derivatives

Ricinine (1), a known major alkaloid in Ricinus communis plant, was used as a starting compound for the synthesis of six ricinine derivatives; two new and four known compounds. The new derivatives; 3-amino-5-methyl-1H-pyrazolo[4,3-c]pyridin-4(5H)-one (2), and 3-amino-5-methyl-1-(phenylsulfonyl)-1H-pyrazolo[4,3-c]pyridin-4(5H)-one (3), as well as the previously prepared derivatives (4–7) were subjected for antimicrobial and antiquorum-sensing evaluation in comparison to different R. communis extracts. Acetyl ricininic acid derivative (5) showed the highest antimicrobial activity among all tested derivatives against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeuroginosa and Candida albicans. However, compound 7 (4-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide) showed the highest antiquorum-sensing activity among all tested compounds and extracts. These findings proved the usefulness of ricinine as a good scaffold for the synthesis of new antimicrobial and antiquorum-sensing derivatives in spite of its poor contribution to the antimicrobial activity of the plant extracts.     

A new naphthalenone isolated from the green walnut husks of Juglans mandshurica Maxim.

Phytochemical study of green walnut husks of Juglans mandshurica Maxim. led to the isolation of a new naphthalenone, (4R)-3,4-dihydro-4-butoxy-5-hydroxy-naphthalen-1(2H)-one (1), together with 16 known compounds. Compounds 4–6, 13, 14 and 17 were isolated from the genus Juglans for the first time, and their chemotaxonomic significance was also evaluated.     

Synthesis and herbicidal activity of novel 6-arylthio-3-methylthio-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones

A series of pyrazolo[3,4-d]pyrimidine-4-one derivatives was conveniently synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphoranes, arylisocyanate, and substituted thiophenols. The structures of the target compounds were confirmed by IR, ¹H NMR, ¹³C NMR, LC-MS, and elemental analysis. The preliminary bioassay demonstrated that some title compounds such as 6-(3-chlorophenylthio)-1-phenyl-3-methylthio-5-(4-chlorophenyl)-1H-pyrazolo[3,4-d]-pyrimidin-4(5H)-one and 6-(4-fluorophenylthio)-1-phenyl-3-methylthio-5-(3-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one showed good inhibition activities against the root of Brassica napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100 mg/L.     

Synthesis of Some New 3-Oxo-2-[(Z)-1-phenylmethylidene]-5H-[1,3]thiazolo[3,2-a]-and N-Acetylated Pyrimidines

3-Oxo-2-[(Z)-1-phenylmethylidene]-5H-[1,3]thiazolo[3,2-a] pyrimidine derivatives 2a–f were synthesized by the reaction of an appropriate 3,4-dihydro-2(H)-pyrimidone 1 , chloroacetic acid, sodium acetate and benzaldehyde. Reaction of 1 with acetic anhydride under heating afforded only 3-N-acetylated 3,4-dihydro-2(H)-pyrimidines 3a–f . The yields of the products after recrystallization from ethanol were of the order of 60–92 %. IR, ¹ H NMR spectroscopy, and elemental analysis were used for the identification of these compounds.     

Synthesis of certain pyrazolo[3,4-d]pyrimidin-3-one nucleosides

Synthesis of the pyrazolo[3,4-d]pyrimidin-3-one congeners of guanosine, adenosine and inosine is described. Glycosylation of 3-methoxy-6-methylthio-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 13 ) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose ( 16 ) in the presence of boron trifluoride etherate gave 3-methoxy-6-methylthio-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 17 ) which, after successive treatments with 3-chloroperoxybenzoic acid and methanolic ammonia, afforded 6-amino-3-methoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4(5H)one ( 18 ). The guanosine analog, 6-amino-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 21 ), was made by sodium iodide-chlorotrimethylsilane treatment of 6-amino-3-methoxy-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4(5H)one ( 19 ), followed by sugar deprotection. Treatment of the adenine analog, 4-amino-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one ( 11 ), according to the high temperature glycosylation procedure yielded a mixture of N-1 and N-2 ribosyl-attached isomers. Deprotection of the individual isomers afforded 4-amino-3-hydroxy-1-βribofuranosylpyrazolo-[3,4-d]pyrimidine ( 26 ) and 4-amino-2-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-3(7H)-one ( 27 ). The structures of 26 and 27 were established by single crystal X-ray diffraction analysis. The inosine analog, 1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 28 ), was synthesized enzymatically by direct ribosylation of 1H-pyrazolo[3,4-d]pyrimidine-3,4(2H,5H)-dione ( 8 ) with ribose-1-phosphate in the presence of purine nucleoside phosphorylase, and also by deamination of 26 with adenosine deaminase.     

Synthesis and calming activity of helicid derivatives containing the 3,4-dihydropyrimidin-2(<Emphasis Type="Italic">H</Emphasis>)-one and 3,4-dihydropyrimidine-2(<Emphasis Type="Italic">H</Emphasis>)-thione moiety

A series of novel helicid derivatives containing 3,4-dihydropyrimidin-2(1H)-one and 3,4-dihydropyrimidine2(1H)-thione moiety (3a–3f and 4a–4f) were synthesized starting from helicid. The structure of the new compounds were characterized by ¹H NMR, IR and HR-MS spectra. The sedative-hypnotic activities of the target compounds were evaluated using the test of spontaneous locomotor activity in mice. All of the derivatives produced moderate to high activities; in particular, compound 4a presented the most potent sedative-hypnotic effect in comparison to the other derivatives, and derivatives 3a, 3c, 3d, 3e and 3f also showed potent activities.     

A Facile and Rapid Method for Preparation of Thiazine and Thiadiazine Derivatives by Sonication Technique

Ultrasound accelerated synthesis of 2,3-(substituted)benzo-1,4-thiazino[5,6-b]-4H-9H-7- methyl-10-oxoquinolines (4), 7-substituted-2,2-dimethyl-2,3-dihydro-1H,10H-phenothiazin- 4-one (5), 4-substituted-3,9, 10-trihydro-11-oxo-quinolino[2,3-b]-1,3,4-thiadiazino[2,3-d]- 1,2,4-triazole (6), and 7,7-dimethyl-7,8-dihydro-3H,5H,6H-1,2,4-triazolo[3,4-b][1,3,4] benzothiadiazin-9-one (7) from carbostyril and dimedone using sulfur powder and iodine as a catalyst in THF is reported. The structures of the compounds have been elucidated on the basis of spectral and elemental analysis.     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Synthesis and antimicrobial activity of new derivatives of pyrano[4',3':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine and new heterocyclic systems

Taking into account previously obtained biological results on some polyheterocyclic compounds (containing different heteroatoms) and in particular on several 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines Ia-v we have carried out the synthesis of twentyone 8-amino-5-isobutyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines 6. Therefore we have slightly modified the structure of the previously studied I introducing at C-5 an isobutyl group instead of the previously examined isopropyl ones in order to see if this variation (changing a little the lipophilicity) will affect the biological activity. Furthermore thieno[3,2-d]pyrimidine-8-thione 7 and their S-alkylated 8 were synthesized. Finally by alkylation of 5-isobutyl-2,2-dimethyl-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-8(9H)-one 3 with alkyl dichlorides (bifunctional reagents) we realized the cyclization of a thiazole or thiazine ring on the [b] side of the pyrimidine ring with formation of the new condensed pentaheterocyclic systems: pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin-8-one 11 and pyrano[4''',3''':4'',5'']pyrido[3'',2'':4',5']thieno[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-8-one 12. It was found that some of the synthesized compounds showed interesting antimicrobial activity (by agar diffusion method) against some gram-positive and gram-negative bacilli strains.     

Two new benzolactones from the leaves of Nicotiana tabacum and their anti-tobacco mosaic virus activities

Two new benzolactones, 5-methyl-6-prenyl-isobenzofuran-1(3H)-one (1), 5-hydroxymethyl-6-prenyl-isobenzofuran-1(3H)-one (2), together with four known phenolic compounds (3–6), were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1–6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compounds 1–6 exhibited high anti-TMV activities with inhibition rates in the range of 16.9–26.2%, respectively.     

离子液体中6-(2,3-环氧丙氧基)-2(1H)-喹啉酮及其衍生物的合成

6-(3-氨基-2-羟基丙基)-2-(1H)-喹啉酮衍生物被发现具有新的正性肌力的活性. 设计合成了一系列新的氨丙醇类喹啉酮化合物. 首先研究了6-羟基-2-(1H)-喹啉酮环氧化物2在离子液体中的合成, 该反应后处理简便, 收率高, 对环境友好. 然后用合成得到的2-(1H)-喹啉酮环氧化合物在离子液体中与一系列具有生物活性的有机碱反应, 合成了氨丙醇类2-(1H)-喹啉酮化合物3. 然后由6-羟基-2-(1H)-喹啉酮出发, 在离子液体中, 进行了一锅法合成氨丙醇类2-(1H)-喹啉酮化合物的研究. 制得的2b, 3b～3f 6个新化合物用IR, ¹H NMR, MS和元素分析进行了结构表征.     

The synthesis of medium-sized cyclic lactams by the intramolecular friedel-crafts cyclization of isocyanates. Formation of novel pyrazolo[3,4-c]benzolactams

A series of 4-ω-phenylalkyl substituted-1H-pyrazol-5-amines has been synthesized from the corresponding α-acetylphenylalkanenitriles and methylhydrazine. They were converted into the corresponding 5-isocyanates and cyclized under Friedel-Crafts conditions to medium-sized cyclic lactams. The reaction was shown to give the 7-, 8-, 9-, and 10-membered lactams but failed to yield the 11-membered lactam. Rings synthesized were: pyrazolo[3,4-c][2]benzazepin-2(1H)-one; 10H-pyrazolo[3,4-c][2]benzazocin-10-one; pyrazolo[3,4-c][2]benzazonin-11(1H)-one; 12H-pyrazolo[3,4-c][2]benzazocin-12-one.