Letters in Organic Chemistry - Volume 15, Issue 8, 2018

Background: In many countries, Pinus species have an important role in economic, trade, culture and traditional medicine. Pinus plants also display diverse bioactivities. Pinus dalatensis Ferré is an endemic species in Vietnam and until now its chemical constituents have not been investigated. Therefore, this study aims to investigate the phytochemistry and antiproliferative activity of isolated compounds from Pinus dalatensis Ferré wood on acute myeloid leukemia (OCI-AML) cells. Methods: Compounds from plant material were isolated by using column chromatography. Their structures were determined by combining spectral analysis and comparison with reported data. Antiproliferative activity in OCI-AML cell line of isolated compounds was carried out by flow cytometry analysis. Results: Fifteen compounds were obtained including two diterpenoids (1, 2), five flavonoids (3, 4, 5, 6, 7), five stilbenoids (8, 9, 10, 11, 12), two lignans (13, 14) and one phenol (15). Compounds 2, 3, and 9 had inhibitory effects on the growth of OCI-AML. Conclusion: This is the first report on the chemical constituents of wood of this endemic species in Vietnam and their biological effects. Moreover, (E)-piceid and vanillic acid 4-β-D-glucopyranoside were isolated from Pinus for the first time.

Background: Oxazinocarbazoles are molecules of particular interest as they possess a broad spectrum of pharmacological activities, such as antiproliferative, antibacterial, antimalarial and antiplasmodial activities. Despite few synthetic methods reported in the literature for their synthesis, there appear to be no reports on the synthesis for oxazinocarbazole fused from simple starting materials. Method: The Mannich condensation of 4-hydroxycarbazole, aldehyde and secondary cyclic amine was carried out to get the corresponding carbazole Mannich base and its subsequent copper(II)acetate catalyzed intramolecular oxidative α-functionaliation of tertiary amine to achieve 1,3-oxazine core. The structures of obtained carbazole Mannich bases and fused oxazinocarbazoles were confirmed by NMR, IR and mass spectra. Results: Various substituted carbazole Mannich bases such as fluoro-, nitro-, dimethoxy-, trimethoxyderivatives reacted smoothly in the presence of copper(II)acetate to give the corresponding fused oxazinocarbazoles in good yields. Conclusion: We have developed a two step method for the synthesis of new oxazino[5,6-c]carbazole derivatives in good yields. This protocol is simple, atom-economic and proceeds smoothly under mild reaction conditions.

A new fluorogenic and chromogenic probe (L) for the selective, sensitive and naked-eye detection of Cu2+ is reported. Complexation constant, complex stoichiometry and quantum chemical (DFT) calculation for Cu2+ complex has been determined. Also, detection limits and the selectivity in front of other divalent and trivalent cations have been evaluated.

In this paper, first graphene oxide catalyzed one-pot three-component green synthesis of 1,3- thiazolidin-4-one using amine, aldehyde and mercapto acetic acid in water has been reported. The reaction is affected via sequential C-N and C-S bond formation and ring transformation reactions leading to thiazolidin-4-ones formation. The use of water as solvent at room temperature, good to excellent yields of pure products (75-92%) and operational simplicity are the salient features of the envisaged protocol. The graphene oxide catalyst is very mild, effective and most of its activity is preserved after being reused for five times.

A simple, green and cost-effective protocol has been devised for the synthesis of 4-substituted-2,6-dimethyl-3,5-pyridinecarboxylates from Hantzsch-type 1,4-dihydropyridines via rapid oxidation in excellent yields using 1.5 equivalent of ceric ammonium nitrate within 15 minutes in solvent-free conditions. The method was able to furnish the products in excellent yields. The products obtained were characterized by their NMR and melting points data.

The copper (I)-catalyzed cross-coupling reactions between aryl halides and guanidines to produce N-aryl guanidines have been developed. Mild reaction conditions, good yields, ligand-free, easy work-up, no column chromatography, and ease of handling at room temperature are the main aspects of the method.

Background: o-Xylylene bis(triethyl ammonium tribromide) (OXBTEATB) as a recyclable and high bromine containing di-(tribromide) reagent has been employed for the bromination of various organic substrates such as phenol and aniline or its derivatives. This catalyst can be recovered and reused several times. Methods: Aryl bromides shown in Table 1, were easily produced from bromination of aromatic compounds by OXBTEATB. This high-yield process lets the reagents to be recycled and reused. Results: As shown in Table 1, substituted anilines, phenols and β-naphthol were found to be the most reactive and immediately converted to the corresponding mono-brominated products by OXBTEATB. Conclusion: OXBTEATB can be considered a solidified bromine. This novel reagent has variable solubility in different polar protic and aprotic solvents but insoluble in non-polar aprotic solvent. Subsequently, OXBTEATB can be recognized as a more useful brominating and regioselective catalyst than the liquid bromine.

Background: Currently perchlorate catalysts gain much attention in organic synthesis due to ease of operation, wide applicability, high yield, and economy. This is evident through increasing number of citation related to their application in industry as well as other allied fields. The aim of this paper is to describe a methodology using lithium perchlorate to catalyze the Knoevenagel condensation reaction for the synthesis of biologically active trans-cinnamic acid in good to excellent yield. Methods: We discuss herein an economic, user-friendly one-pot synthesis of trans-cinnamic acids by refluxing a mixture of a malonic acid with aryl aldehyde in pyridine. The product was easily isolated via filtration and thereafter washed and characterized by spectroscopic methods. Results: This method is robust, stereoselective and high yielding. It can be utilized to synthesize a wide array of trans-cinnamic acids in good to excellent yield using 20% of lithium perchlorate catalyst. It is also useful in the synthesis of aliphatic α,β-unsaturated carboxylic acid. Conclusion: The role of lithium perchlorate as a mild catalyst in the synthesis of trans-cinnamic acid was explored. The reactions afforded a good yield of various products with simpler isolation.

Synthesis of 1,6-anhydro sugars is well known in literature. The dioxolane ring exhibits at least two types of properties. It can be used as a protecting group and reaction site. This work discusses the cleavage of the 1,6-anhydro ring of muramic acid derivatives. To induce the opening of the dioxolane ring in 1,6-anhydro-D-glucose derivatives three types of reagents were used (TFA/Ac2O, Sc(OTf)3/Ac2O, H2SO4/Ac2O). This method is commonly used in sugar chemistry for opening 1,6-anhydro ring. This process led to the preparation of compounds with very good yields (80%, even 98%). In the first attempt the mixture of TFA/Ac2O (1:9) was used. Besides the main product 4, the 3,4-di-Oacetyl- 1,6-anhydro-2-azide-2-deoxy-β-D-glucopyranose was observed as a side product. Main product 4 was obtained as the mixture of α and β (2:1) anomers. Better stereoselectivity was obtained using Sc(OTf)3. In this case, the main product was received with β configuration. The best yield (65%) was obtained using a mixture of H2SO4 and Ac2O and mixture of two anomers of N-acetyl-1,4,6-tri-Oacetyl- 2-deoxy-D-muramic acid ethyl ester was isolated (α and β, 1:4). Depending on which method was used to open dioxolane ring of 1,6-anhydroMur derivative we were able to control the stereochemistry of the reaction and to obtain pure α anomer or mostly β anomer.

Limona-ketone isolated from Cedrus atlantica oil by distillation under reduced pressure was efficiently used as a precursor for the synthesis of newly derived monoarylidenes. Various aldehydes have been used and led to the formation of corresponding compounds in high to excellent yields. The effect of both the nature and the position of the substituted group of the aromatic aldehyde has been investigated.

Background: The interaction between viral HA (hemagglutinin) and oligosaccharide of the host plays an important role in the infection and transmission of avian and human flu viruses, and H5N1 studies showed that the H5N1 duck viruses bound with the highest affinity to trisaccharide Neu5Acα2-3Galβ1-3GlcNAc, H5N1 chicken and human viruses isolated in 1997 in Hong Kong were found to bind the sulfated trisaccharide Neu5Acα2-3Galβ1-4(6-HSO3)GlcNAc with the extraordinary high affinity, and this necessitates the synthesis of sulfated Neu5Acα2-3Galβ1-3GlcNAc library for screening in search of active ligands against of H5N1 virus. Results: Random sulfation of partially protected Neu5Acα2-3Galβ1-3GlcNAc trisaccharide may afford the mono-sulfated and di-sulfated Neu5Acα2-3Galβ1-3GlcNAc libraries for screening their anti-H5N1 activity. In order to synthesize the sulfated library of (Neu5Acα2-3Galβ1-3GlcNAc) trisaccharide, the efficient synthesis of corresponding partially protected Neu5Acα2-3Galβ1-3GlcNAc trisaccharide is an immediate necessity and this target was achieved in an efficient manner. Conclusion: By suitably maneuvering protecting groups on the nitrogen in Galβ1-3GlcNAc related disaccharide acceptors, partially protected Neu5Acα2-3Galβ1-3GlcNAc trisaccharide was efficiently synthesized. It is believed that the strategy followed herein provides a general method for synthesizing useful sialyl acid related oligosaccharides.

Background: Substituted olefins are versatile functional groups and intermediates in chemistry, medicine, electronics, and optics and materials science fields because of their unique properties. One important class of substituted olefins 1,2-diarylethylenes have attracted considerable attention due to their presence in both natural products and pharmacologically active substances. Methods: In this paper, we developed a one-pot two-step coupling reaction of aryl aldehydes, tosylhydrazide with benzyl halides by using inexpensive Pd(PPh3)4 as catalyst, leading to a variety of 1,2- diphenylethenes derivatives with moderate to good yields. Results: The desired 1,2-diarylethylenes were obtained in 46-96% yields via Pd(0)-catalyzed one-pot reaction of benzyl halides, tosylhydrazide, and aryl aldehydes. Conclusion: The catalytic system presented here enables the use of easily accessible starting materials and good functional group tolerance.

The present work describes synthesis of a series of 5-((1-(4-(4-chlorophenyl)thiazol-2-yl)-3- aryl-1H-pyrazol-4-yl)methylene)-2-(arylimino)thiazolidin-4-one derivatives and their molecular docking and biological evaluation as possible antimalarial, anthelmintic and antimicrobial agents. The synthesis of compounds has been accomplished by adopting suitable synthetic methods. Structures of newly synthesized compounds were characterized and authenticated by spectral methods such as IR, 1H-NMR and mass spectra. Synthesized compounds were screened for their in vitro antimicrobial activity against selected bacterial strains and fungal strains viz. B. subtilis, S. aureus, E. coli, P. fluorescens, C. albicans, C. glabrata and antimalarial studies against P. falciparum. Titled compounds were also tested against Pheretima posthuma (earthworm) for their anthelmintic activity. Molecular docking was done to study the binding modes of the potent compounds against Escherichia coli (PDB ID: 1AB4) and Candida P450DM (PDB ID: 1EA1) enzymes. The results revealed that all the compounds exhibited moderate to significant antimicrobial activities. Antimalarial activity screening revealed that one compound 8i showed significant antimalarial activity with of IC50; 0.59 μg/mL as compared to standard drugs chloroquine (IC50= 0.020 μg/mL) and quinine (IC50; 0.268 μg/mL). The most active compound exhibited the mean paralysis time of 19.2 ± 0.9 min and mean death time of 31.7 ± 2.5 min. It can be concluded that some of the synthesized compounds have remarkable antiinfective, antimalarial and anthelmintic activity and are suitable candidates for further scientific exploration.