Letters in Organic Chemistry - Volume 16, Issue 6, 2019

Cu-Fe spinels promoted the Ferrier rearrangement of 2-nitroglycals with several O-nucleophiles. 2,3-Unsaturated carbohydrate derivatives were prepared by the reaction of 3,4,6-tri-Oacetyl- 2-nitroglucal and alcohols in the presence of 5 % of CuFe2O4. After separation of the catalyst with an external magnet, the reaction products were obtained in good yields and high stereo and regioselectivity. Also, S- and heterocyclic C-3 substituted 2-nitro-endo-glycals could be prepared by this method.

A series of novel hydroxy-pyran–chalcone hybrid compounds 4(a-b), 5(a-f), 7(a-b) & 8(a-f) has been synthesized by employing simple methods in various approaches through convergent synthetic strategies. 4-hydroxy-3-acetylcoumarin and 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one have been used as starting materials and were condensed with indole aldehyde, pyrrole aldehydes independently to give the corresponding chalcones. To further explore, alkylation studies have been carried out on the synthesized hybrid chalcones. The synthesized compounds were established on the basis of IR, HRMS, 1HNMR and 13CNMR spectral data.

A series of new phenanthrene-based tylophorine derivatives (PBTs) were synthesized in good yield and their structures were characterized by 1H-NMR spectroscopy and ESI MS. In vitro antitumor activity of these compounds against five human carcinoma cell lines, including HCT116 (colorectal), BGC-823 (gastric), HepG-2 (hepatic), Hela (cervical) and H460 (lung) cells, was evaluated by MTT assay. Among these PBTs, compound 6b showed the highest antitumor activities against HCT116 and HepG-2 cell lines with IC50 values of 6.1 and 6.4 μM, respectively, which were comparable to that of adriamycin hydrochloride. The structure-activity relationship of these compounds was also discussed based on the results of their antitumor activity.

4-Aryl-2-amino-4H-chromenes possessing N,N-dimethylamino group have been reported as potential anticancer drugs. Despite few synthetic methods reported in the literature for their synthesis, there appear to be no reports on the direct use of N,N-dimethyl-3-aminophenol for the synthesis of 4- aryl-2-methylamino-3-nitro-4H-chromenes. One-pot condensation of N,N-dimethyl-3-aminophenol, aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2-nitro-ethenamine was carried out using MW irradiation to get the 4-aryl-2-methylamino-3-nitro-4H-chromenes under catalyst-free conditions. This transformation presumably occurs via o-quinone methide formation, Michael addition-intramolecular O-cyclization-elimination sequence of reactions creating new two C-C bonds and one C-O bond. Various substituted aromatic aldehydes reacted smoothly with N,N-dimethyl-3-aminophenol and (E)-Nmethyl- 1-(methylthio)-2-nitro-ethenamine to give the corresponding 4-aryl-2-methylamino-3-nitro-4Hchromenes in good yields. We have developed a one-pot three component condensation of N,Ndimethyl- 3-aminophenol, aromatic aldehyde and NMSM for the synthesis of N,N-dimethylamino substituted 4-aryl-2-methylamino-3-nitro-4H-chromenes in good yields. The significant features of this reaction include catalyst-free, solvent free, no column chromatographic purification, short reaction time and good yields.

In this report, two new steroidal glycosides were isolated and determined from n-butanol fraction of A.asphodeloides. The structures were confirmed in comparison with the spectral data of known compounds by using different spectroscopic analysis approaches including 1D & 2D-NMR techniques and HRMS. The anti-proliferation screening against cancer cell lines A549 and HeLa indicated that compound 1 exhibited good inhibitory activities with IC50 values of 0.79 and 0.55 μg/mL, respectively.

Two ether and one ester derivatives of the 4-nitro-3-hydroxybenzoic acid were synthesized and characterized. The in vitro antimicrobial and cytotoxic activities of the three novel compounds were also evaluated. The aromatic derivatives showed antibacterial activity against one of the four microorganisms tested and two compounds (C8 and NOBA) had a lower IC50 in HeLa cells.

A method for the synthesis of aryl trifluoroethyl ethers from fluoroalcohols and diaryliodonium salts in the presence of NaH and warm 1,2-dichloroethane has been developed. This transition metal free reaction is mild and facile. Various functional group including electron-withdrawing and electron-donating substrates in the diaryliodonium salts were tolerated in this transformation to afford the products in moderate to high yields.

A proficient, microwave mediated methodology using CuFe2O4 nanoparticle as the catalyst for S-arylation of substituted benzene boronic acids with thiophenol has been developed. In this method, the substituted thioethers were easily obtained through a C-S bond formation using microwave irradiation technique as well as conventional heating in the presence of CuFe2O4 nanoparticles with modest to excellent yields with the less reaction time. The ligand free microwave technique helped in the preparation of substituted thioethers in measurable amount within 10 mins. The same results were obtained with conventional heating in 12h. The reported method is economically efficient and an alternative to the initial existing method for the preparation of substituted thioethers.

An efficient and rapid synthesis of a new class of chiral oxime ethers has been achieved via two-step reaction in which the first step is the reaction of oximes 1a-f with ethyl bromoacetate in the presence of sodium hydride to give oxime ethers 2a-f which are subsequently, in the second step, reacted with different commercially available chiral amines under microwave irradiation conditions to give compounds 3a-l in good to excellent yields. Through this method, we have observed a decrease in reaction time and excellent yields than the previously described conventional method.

The 3+2 cycloaddition reactions are important to generate five-membered heterocyclic compounds as well as altering biological activity effects based on structure. In the study, we synthesized new isoxazoline derivatives of different monoterpenoids and examined the structure analysis using spectroscopical analysis methods, reveal changes in the theoretical analysis related to the biological activity. These new compounds exhibit antioxidant activities; DPPH radical scavenging, ferric reducing, metal chelating activities which are significantly higher than the related commercial monoterpenoids. Theoretical approaches on the compounds containing isoxazole moiety have been performed by the DFT/B3LYP/method, 6-31G(d,p) basis set in the ground state. The global and local chemical reactivity properties of the compounds were investigated by considering the values of electronegativity, global hardness-softness, electronic chemical potential, electrophilicity index and condensed Fukui functions, local softness and local electrophilicity index. Furthermore, total energy, FMOs energy values and the dipole moment (μ), mean polarizability (α), and first order hyperpolarizability (β) values were analysed at the theoretical level to examine the polarizability characteristics of the compounds. The antioxidant activity values of the newly synthesized compounds were compared with a finding of the computational study. The results obtained exhibited good correlation on some parameters.

Efficient steps towards the synthesis of novel (phenyl)(1'-aryl-1,5,5'-triphenyl[3,3'-bi-1Hpyrazol]- 4-yl)methanones 4a-e were developed. The procedure starts from 1-(4-benzoyl-1,5-diphenyl- 1H-3-pyrazolyl)-3-phenyl-2-propyn-1-one (2) which was synthesized by a palladium catalyzed crosscoupling reaction. Compound 2 reacted with various hydrazines to give (E)-(phenyl)[1,5-diphenyl-3- [3-phenyl-1-(2-arylhydrazono)-2-propyn-1-yl]-1H-4-pyrazolyl]methanones E-3a-e. The bis-pyrazole derivatives 4a-e were synthesized from electrophilic cyclization reaction of α,β-acetylenic hydrazones E-3a-e and copper(I) iodide. All synthesized compounds were characterized by FT-IR, 1H, 13C NMR and Mass spectral analyses.

A series of 3-arylspiro[oxirane-2,3'-thiochroman]-4'-one derivatives were synthesized and characterized by spectroscopy like 1H NMR, 13C NMR, mass spectrometry and elemental analysis. They were evaluated for their anti-lung cancer activity on human lung cancer cell line A-549 in DMSO. Compounds under study were found to be potent anti-lung cancer agents with GI50 values less than 10 with respect to positive control adriamycin.