Indium-Catalyzed Aromative Spiro Coupling of Quinones with Oxindoles for Highly Functionalized Xanthenes as Efficient Fluorophores.

A convenient and an efficient protocol for the assembly of diverse xanthenes bearing a biologically interesting oxindole nucleus is developed by utilizing the In(III)-catalyzed spiro coupling of 1,4-benzoquinones or 1,4-naphthoquinones with oxindoles. This novel protocol proceeds via a cascade of double Michael additions and intramolecular cyclization. The synthesized compounds have potential use as fluorophores for the selective imaging of heavy metals in living cells.

Band-Gap Narrowing of Highly Stable Heterogeneous ZrO2 -ZnO Nanocomposites for the Reductive Amination of Carbonyl Compounds with Formic Acid and Triethylamine.

The band gap of a material can be affected by factors such as size, doping materials, and oxygen vacancies. The decrease in band gap and change in state of ZrO2 with the addition of ZnO indicates interfacial interactions between ZrO2 and ZnO in the nanocomposites (NCs), which is further confirmed by the observed shift of the peaks in the Raman spectra. Heterobimetallic ZrO2 -ZnO NCs were synthesized through a sustainable green approach by using sucrose isolated from Angelica gigas Nakai root extract. The highly stable NCs displayed excellent catalytic activity for reductive amination of carbonyl compounds utilizing HCO2 H/(CH3 CH2 )3 N as a hydrogen source. The high catalytic performance of the NCs was closely correlated with the narrow band gap and synergistic effect of ZrO2 with ZnO in the NCs.

Silver(i)/base-promoted propargyl alcohol-controlled regio- or stereoselective synthesis of furan-3-carboxamides and (Z)-enaminones.

A novel and facile regioselective synthesis of furan-3-carboxamides by a silver(i)/base-promoted reaction of propargyl alcohol with 3-oxo amides has been demonstrated. This one-pot protocol provides a rapid synthetic approach to diverse trisubstituted furan-3-carboxamides via cascade nucleophilic addition, intramolecular cyclization, elimination, and isomerization reactions. Employing a substituted propargyl alcohol, (Z)-enaminones have been obtained with high stereoselectivities by a Ag2CO3-promoted reaction starting from 3-oxo amides via C-N bond cleavage.

Regioselective Synthesis of Dihydrothiophenes and Thiophenes via the Rhodium-Catalyzed Transannulation of 1,2,3-Thiadiazoles with Alkenes.

A method for the regioselective synthesis of a wide range of dihydrothiophenes was developed from the rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with aliphatic, aromatic, and heteroaromatic alkenes. Tandem rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with alkenes followed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation was also demonstrated for the one-pot regioselective synthesis of various thiophenes. Advantages of the present method include a broad substrate scope, wide functional group compatibility, and high regioselectivity.

Single electron transfer promoted photoaddition reactions of α-trimethylsilyl substituted secondary N-alkylamines with fullerene C60.

Single electron transfer (SET) promoted photoaddition reactions of secondary N-α-trimethylsilyl-N-alkylamines to C60 were explored to gain a deeper understanding of the mechanistic pathways followed and to expand the library of novel types of organofullerenes that can be generated using this approach. The results show that photoreactions of 10% EtOH-toluene solutions containing C60 and N-α-trimethylsilyl-N-alkylamines produce either aminomethyl-1,2-dihydrofullerenes or symmetric fulleropyrrolidines as major products depending on the nature of alkyl substituents. In contrast, photoreactions of 10% EtOH-ODCB solutions of these amines with C60 mainly lead to the formation of symmetric fulleropyrrolidines. Based on the analysis of product distributions and the results of earlier studies, two feasible mechanistic pathways are proposed for these processes. One route is initiated by SET from the amine substrates to the triplet-excited state of C60 to form the corresponding aminium radicals and C60 anion radicals. EtOH-promoted desilylation of the aminium radicals then takes place to produce aminomethyl radicals which can either add to C60 or couple with the C60 radical anions to form respective radicals or anion precursors of aminomethyl-1,2-dihydrofullerene products. The competing pathway leading to the generation of symmetric fulleropyrrolidines also involves the formation of aminomethyl radicals by using the sequential SET-desilylation process. In this route, the aminomethyl radicals are oxidized by SET to C60 to form iminium ions, which are then transformed to azomethine ylides by a pathway involving a second molecule of the secondary amine. Dipolar cycloaddition of the azomethine ylides to C60 forms the symmetric fulleropyrrolidine cycloadducts. Importantly, the observation that symmetric fulleropyrrolidines are the sole products formed in photoreactions between N-α-trimethylsilyl-N-alkylamines and C60 in 10% EtOH-ODCB has synthetic significance.

Iodine-mediated construction of polyfunctionalized arylazopyrazoles from ß-ketoesters or 2-arylpyrazol-3-ones and arylhydrazines.

This paper describes step-economic iodine-mediated construction of functionalized arylazopyrazoles in the presence of catalytic AgNO3 starting from simple ß-ketoesters and two equivalents of arylhydrazines. This cascade reaction includes in situα-iodination of ß-ketoesters, pyrazol-3-one formation, substitution with a nitrogen nucleophile, and oxidation/aromatization.

Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for (64)Cu Radiotracers.

Bifunctional chelators have been successfully used to construct (64)Cu-labeled radiopharmaceuticals. Previously reported chelators with cross-bridged cyclam backbones have various essential features such as high stability of the copper(II) complex, high efficiency of radiolabeling at room temperature, and good biological inertness of the radiolabeled complex, along with rapid body clearance. Here, we report a new generation propylene-cross-bridged chelator with hybrid acetate/phosphonate pendant groups (PCB-TE1A1P) developed with the aim of combining these key properties in a single chelator. The PCB-TE1A1P was synthesized from cyclam with good overall yield. The Cu(II) complex of our chelator showed good robustness in kinetic stability evaluation experiments, such as acidic decomplexation and cyclic voltammetry studies. The Cu(II) complex of PCB-TE1A1P remained intact under highly acidic conditions (12 M HCl, 90 °C) for 8 d and showed quasi-reversible reduction/oxidation peaks at -0.77 V in electrochemical studies. PCB-TE1A1P was successfully radiolabeled with (64)Cu ions in an acetate buffer at 60 °C within 60 min. The electrophoresis study revealed that the (64)Cu-PCB-TE1A1P complex has net negative charge in aqueous solution. The biodistribution and in vivo stability study profiles of (64)Cu-PCB-TE1A1P indicated that the radioactive complex was stable under physiological conditions and cleared rapidly from the body. A whole body positron emission tomography (PET) imaging study further confirmed high in vivo stability and fast clearance of the complex in mouse models. In conclusion, PCB-TE1A1P has good potential as a bifunctional chelator for (64)Cu-based radiopharmaceuticals, especially those involving peptides.

Volatile compounds and antioxidant capacity of the bio-oil obtained by pyrolysis of Japanese red pine (pinus densiflora siebold and zucc.).

In the present study, sawdust bio-oil (SBO) manufactured by fast pyrolysis of Japanese red pine (Pinus densiflora Siebold and Zucc.) sawdust was analyzed for its volatile chemical compound composition and evaluated for its free radical scavenging potential, inhibition of lipid peroxidation and reducing power. Gas chromatography and mass spectroscopy revealed 29 volatile compounds, comprising 97.6% of the total volatile compounds in SBO. The antioxidant potential of SBO in terms of IC50 values was 48.44 µg/mL for hydroxyl radical scavenging, 89.52 µg/mL for 1,1-diphenyl-2-picrylhydraxyl radical scavenging, 94.23 µg/mL for 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] radical scavenging, and 136.06 µg/mL for superoxide radical scavenging activity. The total phenol content in SBO was 5.7% gallic acid equivalent. Based on the composition of its volatile compounds, high free radical scavenging potential and antioxidant properties, SBO could be used as a source of antioxidant compounds, flavoring agents and nutraceuticals in the food, pharmaceutical, and cosmetic industries.

Anti-tyrosinase, antioxidant, and antibacterial activities of novel 5-hydroxy-4-acetyl-2,3-dihydronaphtho[1,2-b]furans.

Novel 5-hydroxy-4-acetyl-2,3-dihydronaphtho[1,2-b]furans (7a-k) were synthesized using ceric ammonium nitrate (CAN)-catalyzed formal [3 + 2] cycloaddition. Synthesized compounds were evaluated for their tyrosinase inhibitory, antioxidant, and antibacterial activities. A modified spectrophotometric method using l-DOPA as substrate was used to determine tyrosinase inhibitory activities, and a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was used to evaluate antioxidant properties. Antibacterial activities against gram-negative Escherichia coli (KCTC-1924) and gram-positive Staphylococcus aureus (KCTC-1916) were evaluated using the disc diffusion technique. Of the synthesized compounds, 7b with a 4-acetyl and an electron-enriched dihydronaphthofuran ring showed the highest tyrosinase-inhibition activity (IC50 = 8.91 µg/mL), which was comparable with that of standard kojic acid (IC50 = 10.16 µg/mL), potent antioxidant activity (IC50 = 3.33 µg/mL), which was comparable with that of BHT (IC50 = 34.67 µg/mL), and excellent antibacterial activities (MICs: 0.50 µg/mL against E. coli and S. aureus strains). A mechanistic analysis of 7b demonstrated that its tyrosinase inhibitory activity was reversible and competitive. Compounds 7c and 7d showed potent antioxidant activities (IC50: 6.30 and 5.01 µg/mL), and compound 7d also exhibited potent inhibitory activity against E. coli with a MIC of 0.5 µg/mL. Furthermore, compounds 7a, 7e, 7f, and 7i showed potent antibacterial activities against S. aureus with MICs of 0.5 µg/mL, which was comparable to that of ampicillin (MIC = 0.5 µg/mL).

Microwave-assisted synthesis of diverse pyrrolo[3,4-c]quinoline-1,3-diones and their antibacterial activities.

With the aim of developing a general and practical method for library production, a novel and efficient two-phase microwave-assisted cascade reaction between isatins and ß-ketoamides in [Bmim]BF4/toluene was developed for the synthesis of pyrrolo[3,4-c]quinoline-1,3-diones. The features of this methodology are, the use of microwave-assisted rapid synthesis, mild reaction conditions, high yields, operational simplicity, facile product separation, and recyclability. Furthermore, the antibacterial activities of the pyrrolo[3,4-c]quinoline-1,3-dione derivatives produced were evaluated against Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Enterobacter aerogenes) and Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus). These derivatives showed antibacterial activities against Gram-positive strains that were at least equivalent to that against Gram-negative strains. Compound 7{3,5} displayed the most potent antibacterial activity against P. aeruginosa (MIC = 0.5 µg/mL) and greater activity than standard ampicillin (MIC = 1 µg/mL). Compound 7{4,7} exhibited the best inhibitory activity against E. coli and E. aerogenes (MIC = 1 and 0.5 µg/mL), compared with the standard ampicillin (both MICs = 1 µg/mL). The synthesized pyrrolo[3,4-c]quinoline-1,3-diones are expected to be widely used as lead compounds for the development of new antibacterial agents.

Metabolic engineering of Nicotiana benthamiana for the increased production of taxadiene.

We report the production of taxadiene by transformation of N. benthamiana with a taxadiene synthase gene. The production was significantly increased by an elicitor treatment or metabolic pathway shunting. Paclitaxel (Taxol(®)) was first isolated from the bark of the pacific yew tree as an anticancer agent and has been used extensively to treat various types of cancer. Taxadiene, the first committed product of paclitaxel synthesis is cyclized from geranylgeranyl diphosphate (GGPP), and further complex hydroxylation and acylation processes of the unique taxane core skeleton produce paclitaxel. To accomplish de novo production of taxadiene, we transformed Nicotiana benthamiana with a taxadiene synthase (TS) gene. The introduced TS gene under the transcriptional control of the CaMV 35S promoter was constitutively expressed in N. benthamiana, and the de novo production of taxadiene was confirmed by mass spectroscopy profiling. Transformed N. benthamiana homozygous lines produced 11-27 µg taxadiene/g of dry weight. The highest taxadiene production line TSS-8 was further treated with an elicitor, methyl jasmonate, and metabolic pathway shunting by suppression of the phytoene synthase gene expression which resulted in accumulation of increased taxadiene accumulation by 1.4- or 1.9-fold, respectively. In summary, we report that the production of taxadiene in N. benthamiana was possible by the ectopic expression of the TS gene, and higher accumulation of taxadiene could be achieved by elicitor treatment or metabolic pathway shunting of the terpenoid pathway.

Synthesis of novel and diverse mollugin analogues and their antibacterial and antioxidant activities.

Novel and diverse mollugin analogues (1-12) were synthesized using PhB(OH)2/AcOH-mediated electrocyclization reaction as a key step. The newly synthesized compounds were screened for antioxidant and antibacterial activities. Compounds 1, 2, 5, 6, 8, and 10-12 showed high antioxidant activities in DPPH inhibition (IC50=0.52-1.11 µM) compared with BHT (IC50=9.67 µM). Compounds 3 exhibited potent antibacterial activity against Staphylococcus aureus (KCTC-1916) bacterial strain at 100 µg/mL. Structures of newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR data and high-resolution mass spectrometry.

ICl-mediated intramolecular twofold iodoarylation of diynes and diynyl diethers and amines: synthesis of bis(2H-hydronaphthalene and chromene) and 2H-quinoline bearing an alkenyl iodide moiety.

Electrophilic intramolecular twofold iodoarylation was developed from the reaction of diynes and diynyl diethers and amines with iodine monochloride under mild conditions, which produced bis(2H-hydronaphthalene and chromene) and 2H-quinoline bearing an alkenyl iodide moiety in good to excellent yields. These compounds underwent Pd-catalyzed cross-coupling reactions with arylboronic acid and indium tris(arylthiolate) to produce the functionalized styrene derivatives.

Efficient one-pot synthesis of novel and diverse furo[2,3-d] pyrimidinediones and thioxofuro[2,3-d] pyrimidineones by the rhodium (II) pivalate-catalyzed reactions of cyclic diazo compounds.

The rhodium(II)-catalyzed reactions of cyclic diazo compounds derived from barbituric acid or thiobarbituric acid with arylacetylenes and styrenes were examined. These reactions provide a rapid synthetic route to the preparation of a variety of novel and diverse furo [2,3-d pyrimidine-2,4-diones, 2-thioxodihydrofuro [2,3-d pyrimidin-4-ones, dihydrofuro [2,3-d] pyrimidine-2,4-diones, and 2-thioxotetrahydrofuro [2,3-d] pyrimidin-4-ones.

Isolation of a Korean domestic microalga, Chlamydomonas reinhardtii KNUA021, and analysis of its biotechnological potential.

A freshwater microalga, Chlamydomonas reinhardtii KNUA021, was characterized for its potential as a biochemical feedstock. Its optimal growth was observed when the culture was incubated at 25°C and pH 9.4. However, the isolate was capable of survival and growth under a variety of temperatures (10-30°C) and pH (pH 4.0-12.0) conditions. The total lipid content of the isolate was 21.7% of dry weight and it was found that a high-value fatty alcohol, hexadecenol (C(20)H(40)O), was autotrophically produced by strain KNUA021. In addition, a nutritionally important C(18:3) ω3 (α-linolenic acid, ALA) was also identified in this photosynthetic microorganism as one of the major fatty acids. Hence, C. reinhardtii KNUA021 appears to show promise for use in the production of microalgae-based biochemicals.

Non-cross-bridged tetraazamacrocyclic chelator for stable (64)cu-based radiopharmaceuticals.

N-mono/dimethylated TE2A tetraazamacrocycles (MM-TE2A and DM-TE2A) were synthesized in high yields. Both Cu-MM/DM-TE2A complexes showed increased kinetic stability compared to that of Cu-TE2A, whereas Cu-DM-TE2A showed even higher in vitro stability than that of Cu-ECB-TE2A. MM-TE2A and DM-TE2A were quantitatively radiolabeled with (64)Cu ions and showed rapid clearance from the body to emerge as a potential efficient bifunctional chelator.

Gold-catalyzed sequential alkyne activation for the synthesis of 4,6-disubstituted phosphorus 2-pyrones.

Tandem gold-catalyzed addition of alkynyl phosphonic acid monoethyl esters to terminal alkynes and cyclization were developed for the synthesis of 4,6-disubstituted phosphorus 2-pyrones in one reaction vessel based on the concept of sequential alkyne activation. Alkynyl enol phosphonates were selectively obtained through the gold-catalyzed addition reaction in the presence of a catalytic amount of triethylamine. Also, gold-catalyzed cyclization of alkynyl enol phosphonates was successful in giving a variety of 4,6-disubstituted phosphorus 2-pyrones.

Production of taxadiene from cultured ginseng roots transformed with taxadiene synthase gene.

Paclitaxel is produced by various species of yew trees and has been extensively used to treat tumors. In our research, a taxadiene synthase (TS) gene from Taxus brevifolia was used to transform the roots of cultured ginseng (Panax ginseng C.A. Meyer) to produce taxadiene, the unique skeletal precursor to taxol. The TS gene was successfully introduced into the ginseng genome, and the de novo formation of taxadiene was identified by mass spectroscopy profiling. Without any change in phenotypes or growth difference in a TS-transgenic ginseng line, the transgenic TSS3-2 line accumulated 9.1 µg taxadiene per gram of dry weight. In response to the treatment of methyl jasmonate for 3 or 6 days, the accumulation was 14.6 and 15.9 µg per g of dry weight, respectively. This is the first report of the production of taxadiene by engineering ginseng roots with a taxadiene synthase gene.

Silver nanoparticles enhanced luminescence of terbium complex in solution for L-dopa determination.

Luminescent properties of a terbium (Tb3+)-L-3, 4-dihydroxyphenylalanine (L-dopa) complex by binding to colloidal silver nanoparticles (Ag NPs) have been presented. Luminescence intensity of the L-dopa complex was dramatically enhanced about 6-7 times by introducing Ag NPs. The Ag NPs concentration on the luminescent intensity was regarded as a main factor that balancing between an enhancing and a quenching effect of the Ag NPs. It was observed that changing the concentration of L-dopa causes the change in luminescence intensity. Under the optimized condition, the luminescence intensity of the system was linearly related to the concentration of L-dopa. Based on this observation, L-dopa-Tb3+ complex containing Ag NPs has been applied for the determination of L-dopa in pharmaceutical formulation. Linear responses of luminescence intensity were observed in the concentration range of 0.25 to 1.5 nM (r = 0.9934) of L-dopa with limit of detection 0.042 nM. The performance of the system was tested using 1.0 x 10(-9) M of L-dopa, yielding a precision of 1.21% RSD for nine replicate measurements. The present method has been successfully applied to determine L-dopa in pharmaceutical samples.

Enhanced luminescence of lanthanide complexes by silver nanoparticles for ciprofloxacin determination.

We present the enhancement of luminescence of europium complex, Eu(3+)-ciprofloxacin (CIP), in the presence of silver nanoparticles (Ag NPs) for the CIP determination. The increment of the luminescence intensity of the Eu(3+)-CIP complex with Ag NPs was obtained due to the transfer of resonance energy to the fluorophores through the interaction of the excited-state fluorophores and surface plasmon electron in the metal nano surface. The luminescence intensity of Eu3+ was enhanced by complexation with CIP at 614 nm after excitation at 373 nm corresponding to the 5D0-7F2 transitions of Eu3+ ion. Based on the above phenomenon, a sensitive and rapid spectrofluorimetric method has been developed for the CIP determination. Linearity of the calibration curve was obtained in the range of 2.0 x 10(-10)-1.0 x 10(-8) g mL(-1) with correlation coefficient of 0.9992. The limit of detection of CIP was found to be 1.9 x 10(-11) g mL(-1) with the relative standard deviation (RSD) of 1.19% for 5 replicate measurements of 5.0 x 10(-7) g mL(-1) of CIP. The present method has been successfully applied for CIP determination in pharmaceutical and biological samples.