- Design, Synthesis, and Bioactivities of Phthalide and Coumarin Derivatives Based on the Biosynthesis and Structure Simplification of Gossypol
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Because gossypol and hemigossypol show antiviral activity but are structurally complex, we designed and synthesized a series of structurally simpler phthalide and coumarin derivatives. The phthalide derivatives were synthesized by opening the naphthalene ring of hemigossypol, and the coumarin derivatives were synthesized by ring-opening reactions of the phthalide derivatives with the goal of investigating the effect of the lactone ring size on bioactivity. The bioassay results showed that the two series of target compounds possessed moderate to good activities against tobacco mosaic virus, One of the compounds showed in vivo inactivation, curative, and protection activities of 50 ± 1, 53 ± 3, and 48 ± 2% at 500 mg/L, values which are higher than those of gossypol (32 ± 1, 35 ± 1, 29 ± 1%, respectively) and comparable to those of hemigossypol (55 ± 1, 49 ± 1, and 48 ± 1%, respectively) and the commercial antiviral agent ningnanmycin (56 ± 2, 54 ± 1, 58 ± 1%) at the same dose. Thus, this compound is a promising candidate for the development of new anti-plant-virus agents. In addition, most of the synthesized compounds showed broad-spectrum activity when tested against 14 kinds of phytopathogenic fungi and showed selectivity against Sclerotinia sclerotiorum, Physalospora piricola, and Rhizoctonia cerealis. Moreover, some of the compounds exhibited activity against Plutella xylostella larvae; the two most active compounds exhibited larvicidal activities (LC50) of 4.10 and 5.47 mg/L, respectively. Further studies showed that these compounds also exhibited insecticidal activities against Mythimna separata, Helicoverpa armigera, and Pyrausta nubilalis larvae.
- Guo, Zhonglin,Zhou, Pan,Song, Hongjian,Liu, Yuxiu,Zhang, Jingjing,Li, Yongqiang,Wang, Qingmin
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p. 15123 - 15135
(2021/12/27)
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- Transition-metal-free oxidative cyclization reaction of enynals to access pyrane-2-one derivatives
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A novel and efficient metal-free C-H functionalization of enynals is developed to synthesize α-pyrone derivatives via the formation of two C-O bonds. In this project, K2S2O8 has been introduced as an efficient oxygen source and C-H functionalization agent in regioselective oxidative cyclization reaction with a relatively broad substrate scope.
- Abbasi Kejani, Alireza,Ansari, Farzaneh,Armaghan, Mahsa,Balalaie, Saeed,Frank, Walter,Jafarpour, Farnaz,Khosravi, Hormoz
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p. 4263 - 4267
(2021/05/31)
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- Synthesis and vasorelaxant and antiplatelet activities of a new series of (4-Benzylphthalazin-1-ylamino)alcohol derivatives
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A new series of phthalazine derivatives was synthesized by reaction of phthalic anhydride and different substituted phenylacetic acids to yield the benzyliden-3H-isobenzofuran-1-one intermediates 2a–d. Treatment of them with hydrazine afforded 4-benzyl-2H-phthalazin-1-one derivatives 3a–d, which were substituted with the corresponding aminoalkylalcohol to obtain the (4-benzylphthalazin-1-ylamino)alcohol derivatives 4a–h. In general, these phthalazine derivatives relaxed the contractions produced by phenylephrine both in intact or endothelium-denuded aortic rings. In addition, platelet aggregation induced by thrombin was also inhibited by compounds 4c and 4g.
- Munín, Javier,Quezada, Elías,Campos-Toimil, Manuel,Cano, Ernesto,Uriarte, Eugenio,Vi?a, Dolores
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p. 1682 - 1688
(2017/06/27)
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- Triaryl-Like MONO-, BIS-, and TRISKITPHOS Phosphines: Synthesis, Solution NMR Studies, and a Comparison in Gold-Catalyzed Carbon-Heteroatom Bond Forming 5-exo-dig and 6-endo-dig Cyclizations
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A homologous series of triaryl-like KITPHOS-type monophosphines containing one, two, or three bulky 12-phenyl-9,10-dihydro-9,10-ethenoanthracene (KITPHOS) units have been developed, and the influence of increasing steric bulk on their efficacy as ligands in gold(I)-catalyzed carbon-heteroatom bond-forming cyclizations has been investigated. Detailed solution NMR studies on Ph-TRISKITPHOS, its oxide, and the corresponding gold(I) chloride adduct identified a conformational exchange process involving a concerted librational motion of the individual anthracene-derived organic substituents about their P-C bonds. The cessation of this motion at reduced temperatures lowers the molecular symmetry such that the two C6H4 rings in each of the KITPHOS units become inequivalent; a lower energy process involving restricted rotation of the biaryl-like phenyl ring has also been identified. Electrophilic gold(I) complexes of these triaryl-like KITPHOS monophosphines catalyze the 5-exo-dig cycloisomerization of propargyl amides to afford the corresponding methylene oxazolines, which were used in a subsequent tandem carbonyl-ene reaction to afford functionalized 2-substituted oxazolines. A comparative survey revealed that catalyst efficiency for cycloisomerization decreases in the order MONOKITPHOS = BISKITPHOS > PPh3 > TRISKITPHOS. The optimum system also catalyzes the selective 6-endo-dig cyclization of 2-alkynylbenzyl alcohols, 2-alkynylbenzoic acid, and 2-phenylethynyl benzamides; gratifyingly, in several cases the yields obtained are markedly higher and/or reaction times significantly shorter than those previously reported for related gold catalysts. Moreover, these are the first examples of gold(I)-catalyzed 6-endo-dig cycloisomerizations involving 2-phenylethynyl benzamides and, reassuringly, the optimum gold(I)/MONOKITPHOS systems either rivaled or outperformed existing silver or palladium-based catalysts. The steric parameters of this homologous series of phosphines have been quantified and compared with selected triarylphosphines using a combination of Solid-G calculations, to determine the percentage of the metal coordination sphere shielded by the phosphine (the G parameter), and Salerno molecular buried volume calculations (SambVca) to determine the percent buried volume (%Vbur); the corresponding Tolman cone angles have also been determined from correlations.
- Doherty, Simon,Knight, Julian G.,Perry, Daniel O.,Ward, Nicholas A. B.,Bittner, Dror M.,McFarlane, William,Wills, Corinne,Probert, Michael R.
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p. 1265 - 1278
(2016/06/01)
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- Tuning of photoluminescence properties of functional phthalides for OLED applications
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With an objective to develop simple organic systems and tailor their properties for optoelectronic applications, we have synthesized three functionalized phthalide derivatives and have investigated their electroluminescence and photophysical properties under different conditions. These derivatives showed good solubility in common organic solvents and exhibited strong absorption in the range 320–400?nm, having molar extinction coefficient values of ca. 104?M?1?cm?1. The monomeric solution of these derivatives exhibited very low fluorescence quantum yields (ΦF) of ca. 0.003–0.04 owing to their inherent structural features such as intramolecular free rotation and decay to the dark triplet states. However, upon complexation with Lewis acids, such as BCl3, these derivatives showed increased fluorescence quantum yields up to ca. 0.21?±?0.01 and also exhibited aggregation induced emission (AIE) in water/acetonitrile mixtures with the emission yields in the range ca. 0.11–0.16. The morphological analysis of the aggregates through SEM and TEM showed the formation of rod-like structures in 90% water/acetonitrile mixture with an average size of ca. 100?nm. Supporting the observed aggregation induced enhancement in emission properties, these derivatives also exhibited significantly enhanced solid state fluorescence quantum yields of ca. 0.58–0.60. As a representative example, organic light emitting diode (OLED) fabricated using the derivative 3 as the emissive layer showed an efficient electroluminescence centered at 524?nm with a turn on voltage of 9?V, demonstrating thereby their potential use in optoelectronic applications.
- Shanmugasundaram, Madhesh,Joseph, Joshy,Ramaiah, Danaboyina
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p. 156 - 162
(2016/08/15)
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- Design and synthesis of new phthalazinone derivatives containing benzyl moiety with anticipated antitumor activity
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The acetohydrazide derivative reacted with carbon electrophiles such as acid chlorides, acetylacetone, ethyl acetoacetate and aromatic aldehydes to give some interesting heterocyclic compounds. The hydrazide derivative reacted with acetophenone which in turn underwent Vielsmeier-Haack reaction. Also, the phthalazinethione has been synthesized and its behavior towards hydrazine hydrate, oxidizing agent and ethyl chloroacetate has been investigated. The newly synthesized compounds were characterized by spectroscopic data. The antimicrobial, the cytotoxic, and the antioxidant activities of some of the synthesized products were evaluated. Some of the tested compounds showed very strong cytotoxic activity with respect to the standard.
- Marzouk, Magda Ismail,Shaker, Soheir Ahmad,Hafiz, Aisha Ali Abdel,El-Baghdady, Khaled Zakaria
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p. 239 - 251
(2017/02/15)
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- Intramolecular fluorocyclizations of unsaturated carboxylic acids with a stable hypervalent fluoroiodane reagent
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A new class of fluorinated lactones was prepared by the intramolecular fluorocyclizations of unsaturated carboxylic acids by using the stable fluoroiodane reagent in combination with AgBF4. This unique reaction incorporates a cyclization, an aryl migration, and a fluorination all in one step. The fluoroiodane reagent, prepared easily from fluoride, can also be used without a metal catalyst to give moderate yields within just 1 hour, thus demonstrating that it is a suitable reagent for developing new 18F-labelled radiotracers for PET imaging. All in one: A new class of lactones containing a tertiary alkyl fluoride was prepared in high yields by using a stable fluoroiodane reagent. This unique reaction incorporates a cyclization, an aryl migration, and a fluorination all in one step.
- Geary, Gemma C.,Hope, Eric G.,Stuart, Alison M.
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supporting information
p. 14911 - 14914
(2016/02/05)
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- Synthesis of isocoumarins: Rhenium complex-catalyzed cyclization of 2-ethynylbenzoic acids
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When 2-ethynylbenzoic acids were treated with a catalytic amount of a rhenium complex, such as ReCl(CO)5, 6-endo cyclization of 2-ethynylbenzoic acids proceeded with a high selectivity to give the corresponding isocoumarins in moderate to good yields.
- Umeda, Rui,Yoshikawa, Shunya,Yamashita, Kouji,Nishiyama, Yutaka
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p. 2172 - 2179
(2015/12/12)
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- Synthesis of isocoumarins through three-component couplings of arynes, terminal alkynes, and carbon dioxide catalyzed by an NHC-copper complex
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A copper-catalyzed multicomponent coupling reaction between in situ generated ortho-arynes, terminal alkynes, and carbon dioxide was developed to access isocoumarins in moderate to good yields. The key to this CO2-incorporating reaction was the use of a versatile N-heterocyclic carbene/copper complex that was able to catalyze multiple transformations within the three-component reaction.
- Yoo, Woo-Jin,Nguyen, Thanh V. Q.,Kobayashi, Shu
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supporting information
p. 10213 - 10217
(2015/03/31)
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- Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds
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RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 μmol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella typhimurium with MIC = 0.39 and 0.78 μmol/mL, respectively.
- Ibrahim, Hany S.,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.,Elaasser, Mahmoud M.,Abdel-Aziz, Marwa M.
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p. 480 - 486
(2014/09/03)
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- Directing the regioselectivity of rhodium(I) catalysed cyclisation of 2-alkynyl benzoic acids
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Rhodium(I) dicarbonyl complexes 1-4 containing chelating N-donor ligands bis(pyrazolyl)methane (bpm), bis(imidazolyl)methane (bim), tris(pyrazolyl) toluidine (tpt) or tris(imidazolyl)methanol (tim) were investigated as catalysts for the hydroalkoxylation of alkynyl benzoic acids (5a-g). The regioselectivity of the reaction was shown to be highly dependent on the nature of the terminal alkyne substituent (R) of the alkynol substrate. It was also determined that the presence of a third uncoordinated N-donor group in complexes 3 and 4 suppressed the catalytic efficiency of these complexes, and that the selectivity of the reaction for forming either endocyclic (6) or exocyclic (7) hydroalkoxylation products was influenced by the pendant hydroxyl group present in complex 4. We used 13C NMR spectroscopy to quantify the polarity of the alkynyl benzoic acid C≡C bond and our efforts to correlate this measure of bond polarity to the observed regioselectivity of the reaction are discussed.
- Man, Bradley Y.-W.,Knuhtsen, Astrid,Page, Michael J.,Messerle, Barbara A.
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p. 248 - 252
(2013/10/22)
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- Pd-catalysed direct dehydrogenative carboxylation of alkenes: Facile synthesis of vinyl esters
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A novel Pd-catalysed oxidative coupling reaction methodology using readily available carboxylic acids and alkenes for the preparation of vinyl esters has been developed. A broad range of vinyl esters were successfully synthesised. The reactions have demonstrated good efficiency as well as excellent chemo- and regio-selectivity.
- Yang, Dan,Ding, Shixuan,Huang, Jianhui,Zhao, Kang
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supporting information
p. 1211 - 1213
(2013/03/13)
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- Metal-ligand cooperation in the cycloisomerization of alkynoic acids with indenediide palladium pincer complexes
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Indenediide Pd complexes 1a-c are shown to very efficiently catalyze the cycloisomerization of alkynoic acids into alkylidene lactones via metal-ligand cooperation (TON up to 2000). Complexes 1a-c are competent toward a broad range of alkynoic acids, including functionalized and internal ones, and give access to 5- as well as 6- and 7-membered lactones in excellent yields and with very high selectivities.
- Nebra, Noel,Monot, Julien,Shaw, Rosie,Martin-Vaca, Blanca,Bourissou, Didier
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p. 2930 - 2934
(2014/01/06)
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- Copper catalysed domino decarboxylative cross coupling-cyclisation reactions: Synthesis of 2-arylindoles
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The efficient synthesis of 2-arylindoles and 6H-isoindolo[2,1-a]indol-6-one through copper catalysed domino sp-sp2 decarboxylative cross-coupling and subsequent cyclisation reactions of arylpropiolic acids with 2-iodotrifluoroacetanilide has been described. This methodology also demonstrates that indolo[1,2-c]quinazolin-6(5H)-one can be obtained with the elimination of trifluoromethyl anion.
- Ponpandian, Thanasekaran,Muthusubramanian, Shanmugam
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supporting information; experimental part
p. 4248 - 4252
(2012/08/28)
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- A facile and expedient one-pot three-component reaction leading to multifunctionalized stabilized phosphorus ylides
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A three-component reaction between triphenylphosphine, a dialkyl acetylenedicarboxylate and phthalazin-1(2H)-ones that affords novel organic phosphorane derivatives in good to excellent yields is reported. FTIR, 1H, 13C and 31P NMR and elemental analyses have been utilized to characterize the synthesized compounds. Indian Academy of Sciences.
- Hassani, Zahra,Esfandiarpour, Zeinab
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p. 1007 - 1012
(2013/03/13)
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- One-pot synthesis of phthalides via regioselective intramolecular cyclization from ortho-alkynylbenzaldehydes
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A one-pot synthesis of phthalides via an intramolecular 5-exo-dig cyclization of ortho-alkynylbenzaldehydes under mild NaClO2 oxidation conditions is described.
- Li, Jim,Chin, Elbert,Lui, Alfred S.,Chen, Lijing
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scheme or table
p. 5937 - 5939
(2010/11/21)
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- Base-catalyzed intramolecular heterocyclization of o-alkynylbenzhydrazides
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The reaction of methyl o-(2-R-ethynyl)benzoates with hydrazine affords either fused 4-R-methylphthalazin-1-ones or 2-amino-3-R-methylideneisoindolin-1- ones. The latter are on treatment with KOH undergo recyclization into the corresponding 4-R-methylphthalazin- 1-ones.
- Mikhailovskaya,Vasilevsky
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experimental part
p. 632 - 636
(2011/02/17)
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- Metal-free tandem reaction in water: An efficient and regioselective synthesis of 3-hydroxyisoindolin-1-ones
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A mild and effective method was developed for the construction of heterocyclic building blocks 3-hydroxyisoindolin-1-ones via a metal-free tandem transformation with excellent regioselectivity. Significantly, the strategy presents an atom-economical and environmentally friendly transformation, in which two new C-N bonds and one C-O bond are formed in water from two simple starting materials. Moreover, a broad spectrum of substrates can participate in the process effectively to produce the desired products in good yields.
- Zhou, Yu,Zhai, Yun,Li, Jian,Ye, Deju,Jiang, Hualiang,Liu, Hong
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supporting information; experimental part
p. 1397 - 1404
(2010/09/16)
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- Catalytic enantioselective synthesis of chiral phthalides by efficient reductive cyclization of 2-acylarylcarboxylates under aqueous transfer hydrogenation conditions
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A new diamine ligand for asymmetric transfer hydrogenation (ATH) was discovered. The reductive cyclization of 2-acylarylcarboxylates was found to proceed highly stereoselective by the new Ru complex-catalyzed ATH and subsequent In situ lactonization under aqueous conditions. It enables efficient access to a wide variety of 3-substituted phthalides In enantiomerically pure form.
- Zhang, Bo,Xu, Ming-Hua,Lin, Guo-Qiang
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supporting information; experimental part
p. 4712 - 4715
(2009/12/08)
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- The imidazo[2,1-a]isoindole system. A new skeletal basis for antiplasmodial compounds
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The in vitro antiplasmodial activity of some dihydrostilbenamides, phtalazinones, imidazo[2,1-a]isoindole and pyrimido[2,1-a]isoindole derivatives related to the natural dihydrostilbenoid isonotholaenic acid is reported. The evaluation was performed on cultures of F32 strain of Plasmodium falciparum and potent representative compounds were also evaluated in the ferriprotoporphyrin IX biomineralization inhibition test (FBIT). Compounds having the imidazo[2,1-a]isoindole skeleton were the most active and one compound of this group resulted to be as potent as chloroquine, but acting through a mechanism different that of the inhibition of heme biomineralization.
- Del Olmo, Esther,Armas, Marlon Garcia,Ybarra, Ma. Ines,Lopez, Jose Luis,Oporto, Patricia,Gimenez, Alberto,Deharo, Eric,San Feliciano, Arturo
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p. 2769 - 2772
(2007/10/03)
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- Unexpected rearrangements in the synthesis of arylidene- or alkylidene-2-thiophthalides
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Mechanistic studies concerning the reaction by which poly(isothianaphthene) (PITN) is synthesized in one step from commercially available monomers by reacting them with phosphorus pentasulphide (P4S10), have led to the idea of synthesizing a chain-stopper molecule which should give rise to suitable quinoid model compounds for PITN. Within this context benzylidenedithiophthalide and pentylidenedithiophthalide were chosen as target molecules. The unexpected rearrangements and the control of these rearrangements in the synthesis of benzylidenedithiophthalide and pentylidenedithiophthalide are reported.
- Paulussen, Harald,Adriaensens, Peter,Vanderzande, Dirk,Gelan, Jan
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p. 11867 - 11878
(2007/10/03)
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- Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-imidazolyl)alkyl]- 1(2H)-phthalazinones
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A number of 4-substituted 2-[ω-(1-imidazolyl)alkyl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane A2 synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.
- Yamaguchi,Kamei,Koga,Akima,Kuroki,Ohi
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p. 4052 - 4060
(2007/10/02)
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- Incorporation of molecular nitrogen into organic compounds IV. Novel lactam synthesis by nitrogenation of enol lactones
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Enol lactones 7, which are readily prepared from o-haloacetophenone derivatives 15 by palladium-catalyzed carbonylation, react with the titanium-isocyanate complex (1) generated by fixation of CO2 with titanium-nitrogen complex to give the isoindolinone derivatives 8 in good yields.
- Uozumi, Yasuhiro,Mori, Eiko,Mori, Miwako,Shibasaki, Masakatsu
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- Intramolecular Participation in Hypervalent Iodine Oxidation. The Synthesis of Coumaran-3-ones, Aurone, and Isoaurone
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Oxidation of o-hydroxyphenyl alkyl ketones with PhI(OAc)2/KOH-MeOH leads to 2,2-dimethoxycoumaran-3-ones which in the case of o-hydroxy-α-phenylpropiophenone offers a convenient route to aurone and isoaurone.
- Moriarty, Robert M.,Prakash, Om,Prakash, Indra,Musallam, H. A.
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p. 1342 - 1343
(2007/10/02)
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- Atropisomerism in o-Arylacetyl-N,N-dimethylbenzamides
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A series of o-arylacetyl-N,N-dimethylbenzamides, 1-7, being studied as models for chain tautomers, differed markedly in their 1H NMR spectral properties, as a function of the substituents R1-R4.In the two cases where substituents were placed ortho to the amide group, the benzylic protons were anisochronous at ambient temperatures.Reported dynamic 1H NMR results are consistent with concomitant C-N and aryl-CO torsional processes.The 13C carbonyl shifts are compared with those of model compounds.
- Jones, Paul R.,Weisman, Gary R.,Baillargeon, Maurice J.,Gosink, Thomas A.
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p. 3618 - 3620
(2007/10/02)
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