Products 3a Research Articles

Regiodivergent Access to 2- or 3-Substituted Indanones: Catalyst-Controlled Carboacylation via C–C Bond Activation

Indanones are ubiquitous in biologically active compounds. Intramolecular hydroacylation of aldehydes and alkenes is an efficient and atom-economic route to indane rings. However, these reactions a...

Visible-Light-Driven Anti-Markovnikov Hydrocarboxylation of Acrylates and Styrenes with CO 2

Light-driven carbon dioxide (CO2) capture and utilization is one of the most fundamental reactions in Nature. Herein, we report the first visible-light-driven photocatalyst-free hydrocarboxylation ...

Fluorine Effects for Tunable C–C and C–S Bond Cleavage in Fluoro-Julia–Kocienski Intermediates

Classical Julia–Kocienski fluoroolefination represents an indispensable platform for the construction of monofluoroalkenes. Nevertheless, its complex multistep mechanistic manifold along with the u...

Design and synthesis of new benzofuran-1,2,3-triazole hybrid preservatives and the evaluation of their antifungal potential against white and brown-rot fungi

A series of novel benzofuran-1,2,3-triazole hybrids were synthesized and investigated as fungicidal preservatives. The compounds were evaluated for their antifungal potential against white-rot (Trametes versicolor), dry brown-rot (Poria placenta), and wet brown-rot (Coniophora puteana and Gloeophyllum trabeum) fungi, at different concentrations (500 ppm and 1000 ppm). The tests of the final products (8a, 8b, 8c, 8d, 8e, 8f, and 8g) demonstrated that compound N-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)benzofuran-2-carboxamide (8f) at a concentration of 500 ppm was the most active against wet brown-rot C. puteana (23.86% inhibition) and G. trabeum (47.16% inhibition) fungi. However, testing demonstrated that compounds 8a, 8b, 8c, 8d, and 8g at a concentration of 500 ppm did not exhibit acceptable antifungal effects against white-rot T. versicolor and dry brown-rot P. placenta fungi.

Chiral Cobalt(II) Complex Catalyzed Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Selenides with α-Diazo Pyrazoleamides

Organoselenium compounds, due to their high structural diversity, special function, and biological activities, have drawn attention in synthetic chemistry. Herein, a novel example of chiral N,N′-di...

Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies.

Mono- and bis-decylated lumazines have been synthesized and characterized. Namely, mono-decyl chain [1-decylpteridine-2,4(1,3H)-dione] 6a and bis-decyl chain [1,3-didecylpteridine-2,4(1,3H)-dione] 7a conjugates were synthesized by nucleophilic substitution (SN 2) reactions of lumazine with 1-iododecane in N,N-dimethylformamide (DMF) solvent. Decyl chain coupling occurred at the N1 site and then the N3 site in a sequential manner, without DMF condensation. Molecular orbital (MO) calculations show a p-orbital at N1 but not N3 , which along with a nucleophilicity parameter (N) analysis predict alkylation at N1 in lumazine. Only after the alkylation at N1 in 6a, does a p-orbital on N3 emerge thereby reacting with a second equivalent of 1-iododecane to reach the dialkylated product 7a. Data from NMR (1 H, 13 C, HSQC, HMBC), HPLC, TLC, UV-vis, fluorescence and density functional theory (DFT) provide evidence for the existence of mono-decyl chain 6a and bis-decyl chain 7a. These results differ to pterin O-alkylations (kinetic control), where N-alkylation of lumazine is preferred and then to dialkylation (thermodynamic control), with an avoidance of DMF solvent condensation. These findings add to the list of alkylation strategies for increasing sensitizer lipophilicity for use in photodynamic therapy.

Antioxidant, antiproliferative, and acetylcholinesterase inhibition activity of amino alcohol derivatives from 1,4-naphthoquinone

Natural and synthetic naphthoquinones have demonstrated numerous biological activities; therefore, they provide an interesting scaffold for medicinal chemists in the search for new drugs. A series of amino alcohol derivatives from 1,4-naphthoquinone with a free (2a–e) and acetylated (3a–d) hydroxyl group were synthesized, characterized, and evaluated as antioxidant agents employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as acetylcholinesterase (AChE) inhibitors and antiproliferative compounds. In the DPPH assay, compound 3d showed the better result with 51.52% of antioxidant activity at 1 mg/mL, while in ABTS·+ was 2e (47.12%). The antiproliferative activity was evaluated against six different tumor cell lines, where the particular best results were for products 2a, 2c, and 2e against cervix line HeLa, with 50% growth inhibition (GI50) of 5.6, 15.0, and 17.0 μM, respectively. All synthesized compounds presented varying degrees of response, some of them with similar results compared with the positive control 5-fluorouracil. AChE inhibition of the products was not as strong as the positive control galantamine; the most potent compound was 2e with a 50% inhibitory concentration (IC50) of 0.0586 mM, followed by 2a (0.0902 mM). No inhibition in the evaluated concentrations was observed for products 2d and 3a-d. Docking of 2a and 2e was realized against AChE in order to gain insight into the interactions made between them and the enzyme residues in its catalytic gorge. In silico calculations for all synthesized products showed their drug-like properties. Alcohol derivatives, specially 2a and 2e, could be further derivatized in the search for new and improved drugs.

Synthesis, Crystal Structure and Solid State Transformation of 1,2-Bis[(1-methyl-1H-imidazole-2-yl)thio]ethane

The spontaneous S-alkylation of the thyreostatic drug methimazole (1-methyl-1,3-dihydro-1H-imidazole-2-thione, 1) with 1,2-dichloroethane at room temperature, in dark or light conditions, led to the formation of its related substance 1,2-bis[(1-methyl-1H-imidazole-2-yl)thio]ethane, C10H14N4S2 (2a), primarily isolated in the form of dihydrochloride tetrahydrate [C10H16N4S2]Cl2·4(H2O) (2b), which crystallized in the monoclinic P21/c space group. Neutralization of 2b, followed by crystallization from the acetone/water mixture, produced dihydrate C10H14N4S2·2(H2O) (2c), which crystallized in the trigonal R-3 space group. Six water molecules in 2c are H-bonded mutually and to the nitrogen atoms of six molecules of 2a. DSC and TGA showed that 2c melts at 65 °C and loses water up to 120 °C. By cooling to room temperature, anhydrous 2a was obtained. Single crystals of 2a that are suitable for X-ray structure analysis were obtained by neutralization of 2b, followed by crystallization from dry dichloromethane. Anhydrous 2a crystallizes in the monoclinic P21/c space group. The dehydration of 2c led to the formation of the anhydrous product 2a, which is identical to the one obtained by crystallization, as was found by complementary solid-state techniques. No intermediate monohydrate or hemihydrate phases were detected. Powder diffraction showed the same pattern of 2c via both preparation procedures. The structures of all the forms were elucidated by spectroscopy, microscopy and thermal methods and confirmed by single crystal X-ray analysis.

Tetrabutylphosphonium 4-ethoxyvalerate as a biomass-originated media for homogeneous palladium-catalyzed Hiyama coupling reactions

The introduction of a biomass-derived ionic liquid into the Hiyama coupling reactions, which has been considered as a powerful tool for the synthesis of symmetrically and non-symmetrically substituted biaryl structures, could further control or even reduce the environmental impact of this transformation. It was shown that tetrabutylphosphonium 4-ethoxyvalerate, a γ-valerolactone-based ionic liquid, can be utilized as an alternative solvent to create carbon–carbon bonds between aryl iodides and functionalized organosilanes in the presence of 1 mol% Pd under typical Hiyama conditions (130 °C, 24 h, tetrabutylammonium fluoride activator). A comparison of different ionic liquids was performed, and the effects of the catalyst precursor and the moisture content of the reaction mixture on the activity of the catalyst system were investigated. The functional group tolerance was also studied, resulting in 15 cross-coupling products (3a–o) with isolated yields of 45–72% and excellent purity (> 98%).

Tingkat Partisipasi Masyarakat Lokal Dalam Pengembangan Kampung Wisata Kreatif Dago Pojok di Kota Bandung


 
 
 A creative tourism is a form of sustainable tourism that offers authentic experiences of local culture. Tourism activities that have been running for about 9 years in Dago Pojok Creative Village, sparked researchers attention identify the condition of tourism and measuring level of local community participation in the development of Dago Pojok Creative Tourism Village.
 This study aims to identify tourism conditions and level of participation of local communities in the development of Dago Pojok Creative Tourism Village. The types of data used are qualitative and quantitative data with observation, interview and document data collection. Analysis of the data used is descriptive-qualitative data analysis using the concept of tourism components and the theory of a ladder of citizen participation.
 The results of this study show that the condition of tourism which is reviewed through the components of tourism products (4A) in Dago Pojok Creative tourism village recently is sufficient enough to improve some of the existing facilities. The level of community participation in Dago Pojok Creative Tourism Village is at the first level in the theory of a ladder of citizen participation.
 Based on the results, local communities have participated in the development of tourist attractions neverheless but it is still constrained by the government who expects the community itself to develop the tourist village without government assistance. On the contrary, local people expect assistance from the government.
 
 
 
 
 Keyword: participation, rate, community, creative, village
 
 

Semi-synthetic diversification of coronarin D, a labdane diterpene, under Ugi reaction conditions

The prevalence of 5-hydroxydihydrofuran-2(3H)-one moiety in natural products is exploited for the first time using coronarin D, a labdane diterpene, to afford Ugi reaction product 1a and interrupted Ugi product 2a. The potential of the Ugi reaction was further extended to l-phenylalanine, 2-aminopyridine, and d-glucosamine, which afforded Ugi reaction products 3a–f, 4, and 5a–d, respectively. Cytotoxicity studies in RAW cells reveal that compounds 3e and 5b were non-toxic up to 50 µM, and these compounds were able to reduce the LPS stimulated NO production in RAW cells in par with the standard anti-inflammatory drug dexamethasone.

Catalytic Oxidation of Primary C-H Bonds in Alkanes with Bioinspired Catalysts.

Catalytic oxidation of primary C-H bonds of alkanes with a series of iron and manganese catalysts is investigated. Products resulting from oxidation of methylenic sites are observed when hexane (S1) is used as model substrate, while corresponding primary C-H bonds remain unreactive. However, by using 2,2,3,3-tetramethylbutane (S2) as model substrate, which only contains primary alkyl C-H bonds, oxidation takes place catalytically using a combination of hydrogen peroxide, a manganese catalyst and acetic acid as co-catalyst, albeit with modest yields (up to 4.4 TON). Complexes bearing tetradentate aminopyridine ligands provide the best yields, while a related pentadentate ligand provides smaller product yields. The chemoselectivity of the reaction is solvent dependent. Carboxylic acid 2b is observed as major product when the reaction takes place in acetonitrile, because of the facile overoxidation of the first formed alcohol product 2a. Instead the corresponding primary alcohol 2a becomes dominant in reactions performed in 2,2,2-trifluoroethanol (TFE). Polarity reversal of the hydroxyl moiety arising from the strong hydrogen bond donor ability of the latter solvent accounts for the unusual product chemoselectivity of the reaction. The significance of the current results in the context of light alkane oxidation is discussed.

A new perimidine-based fluorescent turn-on chemosensor for selective detection of Cu2+ ions

Two new molecules based on 2-(2-alkoxy-1-naphthyl)-2,3-dihydro-1h-perimidine are synthesized. The binding properties are investigated by fluorescence spectroscopy showing that one of the products (2a) can selectively bind Cu2+ with fluorescence enhancement.

Effect of methyl substituent on the solubility of 1,4-benzoquinone derivatives in n-octanol/water system

The solubility of the compound is a crucial task for new drug design. Quinone is a promising candidate to develop as a new drug. In this research, the synthesis of 1,4-benzoquinone derivatives, that is, 2-(5-bromoamyl)-3,5-dimethyl-1,4-benzoquinone (2a) and 2-(5-bromoamyl)-5-methyl-1,4-benzoquinone (2b) were carried out by decarboxylation and insertion reaction of alkyl bromides. The product 2a and 2b are purified using SiO2 gel column chromatography and analyzed by UV-Visible, FT-IR, and NMR. The yield of 2a is 13.75%, and 2b is 4.04%. The solubility of 2a and 2b, expressed by log P, is measured in the n-octanol/water (3:7 (v/v)) system by the shake flask method. The log P of 2a and 2b are 2.99 and 1.36, respectively. It is showed that the log P of 2a is higher compared to 2b. The presence of two methyl substituents on the quinone ring of 2a supports the increase of hydrophobicity of the compound in the n-octanol/water system.

Modular Synthesis of Diarylalkanes by Nickel-Catalyzed 1,1-Diarylation of Unactivated Terminal Alkenes

A nickel-catalyzed 1,1-diarylation of electronically unbiased alkenes has been developed, providing straightforward access to diarylalkanes from readily available materials. Importantly, both the e...

Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Coumarinylthiazolyl Iminothiazolidinone Hybrids as Potent Urease Inhibitors

AbstractThe present paper is designed to explore the potential of an important class of heterocycles coumarinylthiazolyl iminothiazolidinone to inhibit jack bean urease. The final products 6a–j were prepared by condensation of substituted aldehydes with intermediate 5 in sodium methoxide/methanol mixture. The synthesized compounds were characterized by their FTIR, 1H, 13C NMR and mass spectral data. The synthesized coumarinylthiazolyl iminothiazolidinone hybrids 6 a–j were evaluated for their potential to inhibit urease activity. All the synthesized derivatives showed remarkable inhibitory activity with IC50 ranging 8 to 34 nM, while IC50 of standard thiourea is 18.5 nM. The compound 5‐(2,4‐Dichlorobenzylidene)‐2‐(4‐(2‐oxo‐2H‐chromen‐3‐yl)thiazol‐2‐yl imino) thiazolidin‐4‐one 6 h bearing 2,4‐di‐chloro substituted phenyl ring exhibited excellent activity with IC50 value 8 nM. In silico molecular docking studies was performed against urease enzyme PDBID 4H9 M and predicted possible binding modes in catalytic site for these active compounds. The thiazole nitrogen in compound 6 h formed a strong hydrogen bonding interaction with side chain Gln635 having distance 2.01 Å and rest part of this inhibitor is present close to Val640. The most potent derivative 6 h have highest binding affinity with binding energy −6.178 kcal/mol. It is concluded based upon our results that 6 a and 6 h are most promising compounds from this series and provide a basis for rationale design of most potent urease inhibitors.

Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering.

SummaryThe application of machine learning toward DNA encoded library (DEL) technology is lacking despite obvious synergy between these two advancing technologies. Herein, a machine learning algorithm has been developed that predicts the conversion rate for the DNA-compatible reaction of a building block with a model DNA-conjugate. We exemplify the value of this technique with a challenging reaction, the Pictet-Spengler, where acidic conditions are normally required to achieve the desired cyclization between tryptophan and aldehydes to provide tryptolines. This is the first demonstration of using a machine learning algorithm to cull potential building blocks prior to their purchase and testing for DNA-encoded library synthesis. Importantly, this allows for a challenging reaction, with an otherwise very low building block pass rate in the test reaction, to still be used in DEL synthesis. Furthermore, because our protocol is solution phase it is directly applicable to standard plate-based DEL synthesis.

Structure Elucidation of a Cryptic Condensation Product from Diacetyl and Arylamine - Then and Now.

Some 70 years ago, the reaction of diacetyl (1) and arylamines (2) in hot phosphoric acid was reported to give a new type of condensation products, but no structure was assigned to them. The case is presented to recapitulate the methods and rationales used in classical structure elucidation of organic molecules through reaction networks, before spectroscopic or crystallographic methods were generally available. The difficulties and limits of the classical approach are exemplified through this real-life problem, which could not be solved by the methodology of its time. A representative condensation product 4a has been resynthesized from 1 and p-toluidine (2a), and its structure elucidation by means of 2D NMR techniques is outlined. Keywords.

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemias mediated by cold agglutinins can be divided into cold agglutinin disease (CAD), which is a well-defined clinicopathologic entity and a clonal lymphoproliferative disorder, and secondary cold agglutinin syndrome (CAS), in which a similar picture of cold-hemolytic anemia occurs secondary to another distinct clinical disease. Thus, the pathogenesis in CAD is quite different from that of polyclonal autoimmune diseases such as warm-antibody AIHA. In both CAD and CAS, hemolysis is mediated by the classical complement pathway and therefore can result in generation of anaphylotoxins, such as complement split product 3a (C3a) and, to some extent, C5a. On the other hand, infection and inflammation can act as triggers and drivers of hemolysis, exemplified by exacerbation of CAD in situations with acute phase reaction and the role of specific infections (particularly Mycoplasma pneumoniae and Epstein-Barr virus) as causes of CAS. In this review, the putative mechanisms behind these phenomena will be explained along with other recent achievements in the understanding of pathogenesis in these disorders. Therapeutic approaches have been directed against the clonal lymphoproliferation in CAD or the underlying disease in CAS. Currently, novel targeted treatments, in particular complement-directed therapies, are also being rapidly developed and will be reviewed.

Antimalarial Eudesmane Sesquiterpenoids from Dobinea delavayi.

Eleven new angeloylated eudesmane sesquiterpenoids, dobinins D-N (2, 3, 5, 6, 8, 9, and 11-15), and four known compounds (1, 4, 7, and 10) were isolated from the roots of Dobinea delavayi. A new oxidation product (8a) was also obtained from dobinin H (8). Their structures were elucidated by spectroscopic data and single-crystal X-ray diffraction analyses. Dobinins K-N (12-15) are the first examples of rearrangement noreudesmane analogue sesquiterpenoids with a unique 6/5-fused carbon skeleton. A putative biosynthetic pathway of compounds 12-15 is proposed. Compound 12 exhibited significant antimalarial activity superior to artemisinin with the inhibition ratio of 59.1%, and compounds 3, 5, and 15 exhibited moderate antimalarial activities against Plasmodium yoelii BY265RFP with inhibition ratios ranging from 14.5% to 18.5% at a dose of 30 mg/kg/day. In addition, the apoptosis of P. yoelii BY265RFP by the depolarization of mitochondrial membrane potential with striking ROS production, after parasitized erythrocyte lysis mediated by cytokines IL-12 and IFN-γ, may be a possible mechanism of antimalarial action of compound 12 against P. yoelii BY265RFP.