Photoredox-Catalyzed gem-Difluoromethylenation of Aliphatic Alcohols with 1,1-Difluoroalkenes to Access α,α-Difluoromethylene Ethers.

A switchable synthesis of alcohols and ketones bearing a CF2-OR scaffold using visible-light promotion is described. The method of PDI catalysis is characterized by its ease of operation, broad substrate scopes, and the ability to switch between desired products without the need for transition metal catalysts. The addition or absence of a base plays a key role in controlling the synthesis of the major desired products.

Evaluation of the Free Radical Scavenging Activities of Ellagic Acid and Ellagic Acid Peracetate by EPR Spectrometry.

The purpose of this study was to examine the free radical scavenging and antioxidant activities of ellagic acid (EA) and ellagic acid peracetate (EAPA) by measuring their reactions with the radicals, 2,2-diphenyl-1-picrylhydrazyl and galvinoxyl using EPR spectroscopy. We have also evaluated the influence of EA and EAPA on the ROS production in L-6 myoblasts and rat liver microsomal lipid peroxidation catalyzed by NADPH. The results obtained clearly indicated that EA has tremendous ability to scavenge free radicals, even at concentration of 1 µM. Interestingly even in the absence of esterase, EAPA, the acetylated product of EA, was also found to be a good scavenger but at a relatively slower rate. Kinetic studies revealed that both EA and EAPA have ability to scavenge free radicals at the concentrations of 1 µM over extended periods of time. In cellular systems, EA and EAPA were found to have similar potentials for the inhibition of ROS production in L-6 myoblasts and NADPH-dependent catalyzed microsomal lipid peroxidation.

Development of Sulfonic-Acid-Functionalized Mesoporous Materials: Synthesis and Catalytic Applications.

Sulfonic acid based mesostructures (SAMs) have been developed in recent years and have important catalytic applications. The primary applications of these materials are in various organic synthesis reactions, such as multicomponent reactions, carbon-carbon bond couplings, protection reactions, and Fries and Beckman rearrangements. This review aims to provide an overview of the recent developments in the field of SAMs with a particular emphasis on the reaction scope and advantages of heterogeneous solid acid catalysts.

One-Pot FDCA Diester Synthesis from Mucic Acid and Their Solvent-Free Regioselective Polytransesterification for Production of Glycerol-Based Furanic Polyesters.

A one pot-two step procedure for the synthesis of diethyl furan-2,5-dicarboxylate (DEFDC) starting from mucic acid without isolation of the intermediate furan dicarboxylic acid (FDCA) was studied. Then, the production of three different kinds of furan-based polyesters- polyethylene-2,5-furan dicarboxylate (PEF), polyhydropropyl-2,5-furan dicarboxylate(PHPF) and polydiglycerol-2,5-furandicarboxylate (PDGF)-was realized through a Co(Ac)2·4H2O catalyzed polytransesterification performed at 160 °C between DEFDC and a defined diol furan-based prepolymer or pure diglycerol. In parallel to polymerization process, an unattended regioselective 1-OH acylation of glycerol by direct microwave-heated FDCA diester transesterification led to the formation of a symmetric prepolymer ready for further polymerization and clearly identified by 2D NMR sequences. Furthermore, the synthesis of a more soluble and hydrophilic diglycerol-based furanic polyester was also achieved. The resulting biobased polymers were characterized by NMR, FT-IR spectroscopy, DSC, TGA and XRD. The morphologies of the resulted polymers were observed by FE-SEM and the purity of the material by EDX.

Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides.

The synthesis of novel pyrazolylnucleosides 3a-e, 4a-e, 5a-e, and 6a-e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a-e and 6a-e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI50 9.3 µM) and breast cancer cell line HS 578T (GI50 3.0 µM).

Metal-Free Reduction of Nitrobenzene to Aniline in Subcritical Water.

An environmentally friendly approach for the reduction of nitrobenzene to aniline promoted by carbonaceous bio-based materials was successfully achieved under subcritical water conditions. The proposed methodology features a metal-free process, no-hydrogen input as reductor, the use of commercial bio-based carbon materials having low cost and availability, and water as green solvent under subcritical conditions. Using optimized conditions, reduction of nitrobenzene in the presence of commercial NORIT GAC 12-40 or DACARB PC1000 was accomplished at 310 °C for 6 h and quantitatively furnished the target aniline. Treatment of NORIT GAC 12-40 with KOH allowed to decrease charcoal loading (6 g vs 40 g) and increase aniline yields (80% vs 66%).

Recent Advances in the Microwave-Assisted Production of Hydroxymethylfurfural by Hydrolysis of Cellulose Derivatives-A Review.

The concepts of sustainable development, bioeconomy, and circular economy are being increasingly applied for the synthesis of molecules of industrial interest. Among these molecules, hydroxymethylfurfural as a platform molecule is the subject of various research approaches to improve its synthesis and productivity, and extend its potential uses. Accordingly, this review paper aims essentially at outlining recent breakthroughs obtained in the field of hydroxymethylfurfural production from sugars and polysaccharide feedstocks under microwave-assisted technology. The review discusses advances obtained via microwave activation in major production pathways recently explored, split into the following categories: (i) use of various homogeneous catalysts like mineral or organic acids, metal salts, or ionic liquids; (ii) feedstock dehydration making use of various solid acid catalysts; and (iii) non-catalytic routes.

Chemoenzymatic Synthesis, Nanotization, and Anti-Aspergillus Activity of Optically Enriched Fluconazole Analogues.

Despite recent advances in diagnostic and therapeutic methods in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogues. Anti-Aspergillus activity was observed for an optically enriched derivative, (-)-S-2-(2',4'-difluorophenyl)-1-hexyl-amino-3-(1‴,2‴,4‴)triazol-1‴-yl-propan-2-ol, which exhibits MIC values of 15.6 µg/ml and 7.8 µg/disc in broth microdilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1,000 µg/ml. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analogue exhibited improved antifungal activity against Aspergillus fumigatus (MIC, 1.63 µg/ml). These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotized counterparts, exhibiting anti-Aspergillus activity may have reduced toxicity.

Synthesis of macromolecular systems via lipase catalyzed biocatalytic reactions: applications and future perspectives.

Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions. Biocatalysis can be used in both simple and complex chemical transformations without the need for tedious protection and deprotection chemistry that is very common in traditional organic synthesis. This current review highlights the applicability of one class of biocatalysts viz."lipases" in synthetic transformations, the resolution of pharmaceutically important small molecules including polyphenols, amides, nucleosides and their precursors, the development of macromolecular systems (and their applications as drug/gene carriers), flame retardants, polymeric antioxidants and nanocrystalline solar cells, etc.

Selective Pinacol-Coupling Reaction using a Continuous Flow System.

The first continuous flow pinacol coupling reaction of carbonyl compounds was successfully achieved within only 2 min during a single pass through a cartridge filled with zinc(0). The optimized method allowed the efficient production of gram-scale value-added compounds with high productivity. The developed methodology is efficient for aromatic or α,ß-unsaturated aldehydes but gives moderate results for more stable acetophenone derivatives. Moreover, the flow method displayed better results in terms of yield and selectivity in comparison to the corresponding batch methodology.

Neuroprotective and Antioxidant Activities of 4-Methylcoumarins: Development of Structure-Activity Relationships.

Coumarins are a major class of polyphenols that are abundantly present in many dietary plants and possess different biological activities. Neuroprotective effect of 28 variously substituted 4-methylcoumarins was evaluated in a cell model of oxidative stress-induced neurodegeneration, which measures viability in PC12 cells challenged with hydrogen peroxide by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of these compounds against intracellular reactive oxygen species (ROS) formation was also determined by 2',7'-dichlorofluorescein diacetate method in the same cells. Chemical redox-based assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) tests were employed to explore structure-antioxidant activity relationships in a cell-free environment. The results demonstrated that 4-methylcoumarins containing ortho-dihydroxy or ortho-diacetoxy substituents on the benzenoid ring possess considerable neuroprotective effects. ortho-Dihydroxy compounds inhibited cytotoxicity (44.7-62.9%) and ROS formation (41.6-71.1%) at 50 µM and showed considerable antioxidant effects. We conclude that 4-methylcoumarins are promising neuroprotective and antioxidant scaffolds potentially usefull for management of neurodegenerative diseases.

Synthesis and anti-inflammatory activity evaluation of novel triazolyl-isatin hybrids.

New isatin-triazole based hybrids have been synthesized and evaluated for their inhibitory activity of TNF-α induced expression of Intercellular Adhesion Molecule-1 (ICAM-1) on the surface of human endothelial cells. Structure-activity relationship (SAR) studies revealed that the presence of the electron-attracting bromo substituent at position-5 of the isatin moiety played an important role in enhancing the anti-inflammatory potential of the synthesized compounds. Z-1-[3-(1H-1,2,4-Triazol-1-yl)propyl]-5-bromo-3-[2-(4-methoxyphenyl)hydrazono]indolin-2-one (19) with an IC50 = 20 µM and 89% ICAM-1 inhibition with MTD at 200 µM was found to be the most potent of all the synthesized derivatives. Introduction of 1,2,4-triazole ring and electron-donating methoxy group on the phenylhydrazone moiety resulted in four-fold increase of the anti-inflammatory activity.

Furfural Production from d-Xylose and Xylan by Using Stable Nafion NR50 and NaCl in a Microwave-Assisted Biphasic Reaction.

Pentose dehydration and direct transformation of xylan into furfural were performed in a water-cyclopentyl methyl ether (CPME) biphasic system under microwave irradiation. Heated up between 170 and 190 °C in the presence of Nafion NR50 and NaCl, d-xylose, l-arabinose and xylan gave furfural with maximum yields of 80%, 42% and 55%, respectively. The influence of temperature and reaction time on the reaction kinetics was discussed. This study was also completed by the survey of different reactant ratios, such as organic layer-water or catalyst-inorganic salt ratios. The exchange between proton and cation induced by an excess of NaCl was monitored, and a synergetic effect between the remaining protons and the released HCl was also discovered.

Chemo-Enzymatic Synthesis of Oligoglycerol Derivatives.

A cleaner and greener method has been developed and used to synthesize 14 different functionalized oligomer derivatives of glycerol in moderate 29%-39% yields over three steps. After successive regioselective enzymatic acylation of the primary hydroxyl groups, etherification or esterification of the secondary hydroxyl groups and chemoselective enzymatic saponification, the target compounds can efficiently be used as versatile building blocks in organic and supramolecular chemistry.

Biocatalytic Synthesis of Novel Partial Esters of a Bioactive Dihydroxy 4-Methylcoumarin by Rhizopus oryzae Lipase (ROL).

Highly regioselective acylation has been observed in 7,8-dihydroxy-4-methylcoumarin (DHMC) by the lipase from Rhizopus oryzae suspended in tetrahydrofuran (THF) at 45 °C using six different acid anhydrides as acylating agents. The acylation occurred regioselectively at one of the two hydroxy groups of the coumarin moiety resulting in the formation of 8-acyloxy-7-hydroxy-4-methylcoumarins, which are important bioactive molecules for studying biotansformations in animals, and are otherwise very difficult to obtain by only chemical steps. Six monoacylated, monohydroxy 4-methylcoumarins have been biocatalytically synthesised and identified on the basis of their spectral data and X-ray crystal analysis.

Selective Pinacol Coupling on Regeneratable Supported Acids in Sole Water.

Efficient pinacol coupling was developed in sole water, using a reusable heterogeneous supported acid source and zinc as cheap available metal source. This medium can be easily regenerated up to 10-fold without loss of activity. Moreover, supported acids enhance the selectivity of the pinacol coupling reaction compared with homogeneous acids.

Synthesis of C-arylnucleoside analogues.

Modified nucleoside analogues are of great biological importance as antiviral and antitumoral agents. There is special interest in the preparation of C-aryl nucleosides with an aromatic ring in different positions of the glycone for their biological activity. Different chemical synthesis strategies for these targets are described in this review.

Micellar catalysis using a photochromic surfactant: application to the Pd-catalyzed Tsuji-Trost reaction in water.

The first example of a Pd-catalyzed Tsuji-Trost reaction, applied in a photochromic micellar media under conventional heating and microwave irradiation, is reported. The surfactant activity and recycling ability were investigated and compared with those of a few commercially available surfactants. The synthetic photochromic surfactant proved to be efficient, recyclable, and versatile for Pd-catalyzed coupling reactions.

High-affinity RNA targeting by oligonucleotides displaying aromatic stacking and amino groups in the major groove. Comparison of triazoles and phenyl substituents.

Three 5-modified 2'-deoxyuridine nucleosides were synthesized and incorporated into oligonucleotides and compared with the previously published 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W. The introduction of an aminomethyl group on the phenyl group led to monomer X, which was found to thermally stabilize a 9-mer DNA:RNA duplex, presumably through the partial neutralization of the negative charge of the backbone. By also taking advantage of the stacking interactions in the major groove of two or more of the monomer X, an extremely high thermal stability was obtained. A regioisomer of the phenyltriazole substituent, that is the 5-(4-phenyl-1,2,3-triazol-1-yl)-2'-deoxyuridine monomer Y, was found to destabilize the DNA:RNA duplex significantly, but stacking in the major groove compensated for this when two to four monomers were incorporated consecutively. Finally, the 5-phenyl-2'-deoxyuridine monomer Z was incorporated for comparison, and it was found to give a more neutral influence on duplex stability indicating less efficient stacking interactions. The duplexes were investigated by CD spectroscopy and MD simulations.

Synthesis and characterization of a new photoinduced switchable ß-cyclodextrin dimer.

This paper reports an efficient preparation of bridged bis-ß-CD AZO-CDim 1 bearing azobenzene as a linker and exhibiting high solubility in water. The photoisomerization properties were studied by UV-vis and HPLC and supported by ab initio calculations. The cis/trans ratio of AZO-CDim 1 is 7:93 without irradiation and 37:63 after 120 min of irradiation at 365 nm; the reaction is reversible after irradiation at 254 nm. The photoinduced, switchable binding behavior of AZO-CDim 1 was evaluated by ITC, NMR and molecular modeling in the presence of a ditopic adamantyl guest. The results indicate that AZO-CDim 1 can form two different inclusion complexes with an adamantyl dimer depending on its photoinduced isomers. Both cavities of cis-AZO-CDim 1 are complexed simultaneously by two adamantyl units of the guest forming a 1:1 complex while trans-AZO-CDim 1 seems to lead to the formation of supramolecular polymers with an n:n stoichiometry.