P-methoxybenzyl Alcohol Research Articles

Evaluation of Transiently O-6-Protected Guanosine Morpholino Nucleosides in Phosphorodiamidate Morpholino Oligonucleotide Synthesis

AbstractA novel strategy is presented for the synthesis of morpholino guanosine monomers protected at O-6 with 1-(4-azidophenyl)ethan-1-ol, p-methoxybenzyl alcohol and trimethylsilylethyl groups. The introduction of these protecting groups increases the solubility of the morpholino nucleosides which is crucial during the synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs). HPLC analysis shows that the trimethylsilylethyl-protected monomer gives better coupling efficiency in PMO synthesis compared to the regular monomer. Moreover the nonpolar nature of the O-6-protected monomer facilitates the preparation of guanosine-rich oligomer in solution.

The Accuracy of Diagnosis and Genotyping of Leishmania Species Based on Spliced Leader Mini-Exon Gene by Nuclear Magnetic Resonance and Sequencing Assays.

We aimed to evaluate the accuracy of genotyping of Leishmania species by the spliced leader mini-exon gene. Suspected leishmaniasis patients, referred to Masieh Daneshvary Hospital, Tehran, Iran were included from May 2017 to September 2021. The Leishmania species were genotyped by PCRRFLP based on the SL mini-exon gene and the ITS1 region of SSU-rRNA gene and compared with the sequencing results. The expressed metabolites of metacyclic promastigotes were evaluated by Proton nuclear magnetic resonance (1H-NMR). Out of 66 suspected cases, 36 (54.4%) were positive for Leishmania species based on the PCR assays. In 21 (31.8%) cases, promastigotes grew on culture tubes. Based on the RFLP of SL RNA profile, 13 (19.7%) L. tropica, 9 (13.6%) L. major, 3 (4.5%) L. infantum, and 8 (12.1%) C. fasciculata isolates, isolated from culture media, were identified; however, 3 (4.5%) cases were unidentifiable due to the low number of parasites. Seventeen metabolites were expressed by the metacyclic forms of L. major, L. tropica and C. fasciculata isolates. The top differential metabolites expressed more in C. fasciculata were FAD, p-Methoxybenzyl alcohol and S-b-G-5, 5-G-b-S (A = CH2) (P<0.005) whereas Veratryl glycerols and D-(+)-Mannose were significantly increased in L. major and Betulin, LTyrosine in L. tropica (P<0.01). The invaluable techniques such as sequencing and 1H-NMR confirmed the results of genotyping of Leishmania species based on the SL mini-exon gene. SL mini exon gene can be used as a diagnostic tool to differentiate various Leishmania genotypes and detect contamination of culture media with C. fasciculata.

Catalytic Reductive Amination of Aromatic Aldehydes on Co-Containing Composites

The performance of a series of cobalt-based composites in catalytic amination of aromatic aldehydes by amines in the presence of hydrogen as well as hydrogenation of quinoline was studied. The composites were prepared by pyrolysis of CoII acetate, organic precursor (imidazole, 1,10-phenantroline, 1,2-diaminobenzene or melamine) deposited on aerosil (SiO2). These composites contained nanoparticles of metallic Co together with N-doped carboneous particles. Quantitative yields of the target amine in a reaction of p-methoxybenzaldehyde with n-butylamine were obtained at p(H2) = 150 bar, T = 150 °C for all composites. It was found that amination of p-methoxybenzaldehyde with n-butylamine and benzylamine at p(H2) = 100 bar, T = 100 °C led to the formation of the corresponding amines with the yields of 72–96%. In the case of diisopropylamine, amination did not occur, and p-methoxybenzyl alcohol was the sole or the major reaction product. Reaction of p-chlorobenzaldehyde with n-butylamine on the Co-containing composites at p(H2) = 100 bar, T = 100 °C resulted in the formation of N-butyl-N-p-chlorobenzylamine in 60–89% yields. Among the considered materials, the composite prepared by decomposition of CoII complex with 1,2-diaminobenzene on aerosil showed the highest yields of the target products and the best selectivity in all studied reactions.

A Light(er) Approach for the Selective Hydrogenation of 5-Hydroxymethylfurfural to 2,5-Bis(hydroxymethyl)furan without External H2.

The selective conversion of 5-hydroxymethyfurfural (HMF), a biomass-derived platform molecule, to value added chemicals can ease the burden on petroleum-based fine chemical synthesis. The active contribution of renewable energy sources along with low cost, environmental friendliness, and a simple reaction system must be adopted for better sustainability. In this context, photocatalytic selective hydrogenation of HMF to 2,5-bis(hydroxymethyl)furan (BHMF) was achieved over P25 titania nanoparticles without chemical squander. Simultaneously the photo-oxidation of p-methoxybenzyl alcohol (MeOBA) to p-methoxybenzaldehyde (MeOBaL), similar to biomass-derived vanillin, was carried out, abolishing the need of additional redox reagents. This system put forward the competent employment of photogenerated excitons for the valorization of lignocellulosic biomass to fine chemicals, which is an urgent requirement for sustainable chemical synthesis.

Ultra-low content of Pt modified CdS nanorods: Preparation, characterization, and application for photocatalytic selective oxidation of aromatic alcohols and reduction of nitroarenes in one reaction system.

A series of Pt nanoparticles (with size of 3-4 nm) decorated CdS nanorods were prepared via a simple solvothermal method. The samples were then used for photocatalytic selective oxidation (SO) of aromatic alcohols and reduction (SR) of nitroarenes in one reaction system. The platinized samples showed enhanced activity for the conversions than pristine CdS as Pt can serve as e- trapping and reaction sites, by which the recombination of photoinduced charge carriers can be suppressed and the adsorption of reactants and the SR of nitroarenes can be promoted. The sample loaded with only of 0.03% Pt showed the highest performance and, after irradiation for 4 h, the conversions of p-methoxybenzyl alcohol and nitrobenzene are as high as 92.7% and 94.8%, while the yields of p-methoxybenzaldehyde and aniline are 80.5% and 36.0%. The activities are about 2.0 times higher than that of CdS. The coupling reaction mechanism for the SO of aromatic alcohols to aldehydes and SR of nitroarenes to anilines in the reaction system was finally proposed.

Stepwise Hydrogen Atom and Proton Transfers in Dioxygen Reduction by Aryl-Alcohol Oxidase.

The mechanism of dioxygen reduction by the flavoenzyme aryl-alcohol oxidase was investigated with kinetic isotope, viscosity, and pL (pH/pD) effects in rapid kinetics experiments by stopped-flow spectrophotometry of the oxidative half-reaction of the enzyme. Double mixing of the enzyme in a stopped-flow spectrophotometer with [α-2H2]- p-methoxybenzyl alcohol and oxygen at varying aging times established a slow rate constant of 0.0023 s-1 for the wash-out of the D atom from the N5 atom of the reduced flavin. Thus, the deuterated substrate could be used to probe the cleavage of the N-H bond of the reduced flavin in the oxidative half-reaction. A significant and pH-independent substrate kinetic isotope effect (KIE) of 1.5 between pH 5.0 and 8.0 demonstrated that H transfer is partially limiting the oxidative half-reaction of the enzyme; a negligible solvent KIE of 1.0 between pD 5.0 and 8.0 proved a fast H+ transfer reaction that does not contribute to determining the flavin oxidation rates. Thus, a mechanism for dioxygen reduction in which the H atom originating from the reduced flavin and a H+ from a solvent exchangeable site are transferred in separate kinetic steps is proposed. The spectroscopic and kinetic data presented also showed a lack of stabilization of transient flavin intermediates. The substantial differences in the mechanistic details of O2 reduction by aryl-alcohol oxidase with respect to other alcohol oxidases like choline oxidase, pyranose 2-oxidase, and glucose oxidase further demonstrate the high level of versatility of the flavin cofactor in flavoenzymes.

Anti-inflammatory effects of anisalcohol on lipopolysaccharide-stimulated BV2 microglia via selective modulation of microglia polarization and down-regulation of NF-κB p65 and JNK activation

Inflammation plays a pivotal role in the pathogenesis of ischemic stroke. The inhibition of inflammation appears to be a potential therapeutic strategy for neuro-inflammatory injury after ischemic stroke. In response to cerebral ischemia, resident microglia and infiltrated macrophages from the damaged blood–brain barrier are activated. Microglia activation appears to be a double-edged sword. Activated microglia migrate to the damaged neuron, change their phenotype to M1 or M2, and become involved in nerve damage and repair. M1 phenotype microglia express multiple inflammatory factors to exacerbate secondary brain injury, while those of M2 phenotype release anti-inflammatory factors to promote brain recovery after ischemic stroke. Therefore, the regulation of microglia M1/M2 phenotype after ischemic stroke is crucial for brain repair. The present study aimed to investigate the anti-inflammatory effect of anisalcohol (p-methoxybenzyl alcohol, PMBA), a phenolic compound from Gastrodia elata Blume, which has been shown to reduce cerebral ischemic injury in rodents. However, no studies have specifically addressed whether PMBA can selectively modulate microglia polarization. In this study, lipopolysaccharide-stimulated BV2 microglia were used to assess the anti-inflammatory effect of PMBA. The results revealed that PMBA significantly reduced the lipopolysaccharide-induced production of tumour necrosis factor α, prostaglandin E2, and nitric oxide, without causing cell toxicity. In addition, it increased anti-inflammatory interleukin-10 and transforming growth factor-β. Phenotypic analysis of LPS-stimulated BV2 microglia showed that PMBA significantly down-regulated the expression of the M1 marker CD16/32 and up-regulated that of the M2 marker CD206. Moreover, PMBA suppressed NF-κB activation and inhibited the phosphorylation of JNK in LPS-stimulated BV2 microglia. Collectively, our data demonstrate that PMBA can inhibit M1 transformation and promote M2 transformation of microglia, thus attenuating the production of inflammatory mediators and cytokines. The modulation of microglia M1/M2 polarization may involve multiple mechanisms, mainly, the inhibition of NF-κB and MAPK activation. These findings suggest that PMBA acts as an anti-inflammatory factor and is a possible therapeutic candidate for diseases such as ischemic stroke, where inflammation is a central hallmark.

In vitro alternatives: Evaluation and recommendations for the reconstructed 3D skin micronucleus assay (RSMN assay): 72h protocol

Three compounds with nitrocarbazole frameworks were synthesized and their electrochemical reversibility as organic electrocatalysts was studied by cyclic voltammetry. The electrochemical reversibility and oxidation-reduction potential of the compounds were greatly affected by their substituents. The oxidation-reduction potential of the compound with an electron-donating group was negative, while that of the compound with an electron-withdrawing group on the carbazole framework was positive. The electrocatalytic oxidation activities of the nitrocarbazole compounds were investigated through cyclic voltammetry and controlled potential electrolysis at room temperature. The electrocatalysts showed excellent selectivity for p-methoxybenzyl alcohol, converting it to the corresponding aldehyde through electro-oxidation with just 2.5 mol% of the electrocatalysts presented. The electrocatalysts maintained their excellent electroredox activity following recycling.

Synthesis of nitrocarbazole compounds and their electrocatalytic oxidation of alcohol

Three compounds with nitrocarbazole frameworks were synthesized and their electrochemical reversibility as organic electrocatalysts was studied by cyclic voltammetry. The electrochemical reversibility and oxidation-reduction potential of the compounds were greatly affected by their substituents. The oxidation-reduction potential of the compound with an electron-donating group was negative, while that of the compound with an electron-withdrawing group on the carbazole framework was positive. The electrocatalytic oxidation activities of the nitrocarbazole compounds were investigated through cyclic voltammetry and controlled potential electrolysis at room temperature. The electrocatalysts showed excellent selectivity for p-methoxybenzyl alcohol, converting it to the corresponding aldehyde through electro-oxidation with just 2.5 mol% of the electrocatalysts presented. The electrocatalysts maintained their excellent electroredox activity following recycling.

Eletrodos de feltro de carbono modificados com filme dimérico de rutênio: aplicação em oxidações eletroquímicas de álcoois

Foram preparados filmes poli-[(H2O)(L)2Ru-O-Ru(L)2(OH2)]4+(L=4-metil-4 ́-pirrol-1-il-butil-2,2 ́-bipiridina)(poli-dim.), sobreeletrodos de feltro de carbono por eletropolimerização anódica direta do monômero. Esses eletrodos de feltro de carbono modificados por deposição desses filmes foram utilizados como eletrocatalisadores em oxidações de álcoois, a potencial constante de +1,15 V (vs ECS), em pH 1,0 e 6,8. Os álcoois utilizados e seus produtos de oxidação foram: álcool benzílico (benzaldeído), cicloexanol (cicloexanona), 1-feniletanol (acetofenona) e álcool p-metoxibenzílico (p-metoxibenzaldeído). As reações revelaram-se seletivas na obtenção dos produtos com bons rendimentos.

Radiation processing of thermoplastic starch by blending aromatic additives: Effect of blend composition and radiation parameters

This paper reports on the effects of electron beam (EB) irradiation on poly α-1,4-glucose oligomers (maltodextrins) in the presence of water and of various aromatic additives, as model blends for gaining a better understanding at a molecular level the modifications occurring in amorphous starch–lignin blends submitted to ionizing irradiation for improving the properties of this type of bio-based thermoplastic material. A series of aromatic compounds, namely p-methoxy benzyl alcohol, benzene dimethanol, cinnamyl alcohol and some related carboxylic acids namely cinnamic acid, coumaric acid, and ferulic acid, was thus studied for assessing the ability of each additive to counteract chain scission of the polysaccharide and induce interchain covalent linkages. Gel formation in EB-irradiated blends comprising of maltodextrin was shown to be dependent on three main factors: the type of aromatic additive, presence of glycerol, and irradiation dose. The chain scission versus grafting phenomenon as a function of blend composition and dose were studied using Size Exclusion Chromatography by determining the changes in molecular weight distribution (MWD) from Refractive Index (RI) chromatograms and the presence of aromatic grafts onto the maltodextrin chains from UV chromatograms. The occurrence of crosslinking was quantified by gel fraction measurements allowing for ranking the cross-linking efficiency of the additives. When applying the method to destructurized starch blends, gel formation was also shown to be strongly affected by the moisture content of the sample submitted to irradiation. The results demonstrate the possibility to tune the reactivity of tailored blend for minimizing chain degradation and control the degree of cross-linking.

Stereoselective Hydride Transfer by Aryl‐Alcohol Oxidase, a Member of the GMC Superfamily

Primary alcohol oxidation by aryl-alcohol oxidase (AAO), a flavoenzyme providing H(2) O(2) to ligninolytic peroxidases, is produced by concerted proton and hydride transfers, as shown by substrate and solvent kinetic isotope effects (KIEs). Interestingly, when the reaction was investigated with synthesized (R)- and (S)-α-deuterated p-methoxybenzyl alcohol, a primary KIE (≈6) was observed only for the R enantiomer, revealing that the hydride transfer is highly stereoselective. Docking of p-methoxybenzyl alcohol at the buried crystal active site, together with QM/MM calculations, showed that this stereoselectivity is due to the position of the hydride- and proton-receiving atoms (flavin N5 and His502 Nε, respectively) relative to the alcohol Cα-substituents, and to the concerted nature of transfer (the pro-S orientation corresponding to a 6 kcal mol(-1) penalty with respect to the pro-R orientation). The role of His502 is supported by the lower activity (by three orders of magnitude) of the H502A variant. The above stereoselectivity was also observed, although activities were much lower, in AAO reactions with secondary aryl alcohols (over 98 % excess of the R enantiomer after treatment of racemic 1-(p-methoxyphenyl)ethanol, as shown by chiral HPLC) and especially with use of the F501A variant. This variant has an enlarged active site that allow better accommodation of the α-substituents, resulting in higher stereoselectivity (S/R ratios) than is seen with AAO. High enantioselectivity in a member of the GMC oxidoreductase superfamily is reported for the first time, and shows the potential for engineering of AAO for deracemization purposes.

Fungal aryl-alcohol oxidase: a peroxide-producing flavoenzyme involved in lignin degradation

Aryl-alcohol oxidase (AAO) is an extracellular flavoprotein providing the H(2)O(2) required by ligninolytic peroxidases for fungal degradation of lignin, the key step for carbon recycling in land ecosystems. O(2) activation by Pleurotus eryngii AAO takes place during the redox-cycling of p-methoxylated benzylic metabolites secreted by the fungus. Only Pleurotus AAO sequences were available for years, but the number strongly increased recently due to sequencing of different basidiomycete genomes, and a comparison of 112 GMC (glucose-methanol-choline oxidase) superfamily sequences including 40 AAOs is presented. As shown by kinetic isotope effects, alcohol oxidation by AAO is produced by hydride transfer to the flavin, and hydroxyl proton transfer to a base. Moreover, site-directed mutagenesis studies showed that His502 activates the alcohol substrate by proton abstraction, and this result was extended to other GMC oxidoreductases where the nature of the base was under discussion. However, in contrast with that proposed for GMC oxidoreductases, the two transfers are not stepwise but concerted. Alcohol docking at the buried AAO active site resulted in only one catalytically relevant position for concerted transfer, with the pro-R α-hydrogen at distance for hydride abstraction. The expected hydride-transfer stereoselectivity was demonstrated, for the first time in a GMC oxidoreductase, by using the (R) and (S) enantiomers of α-deuterated p-methoxybenzyl alcohol. Other largely unexplained aspects of AAO catalysis (such as the unexpected specificity on substituted aldehydes) can also be explained in the light of the recent results. Finally, the biotechnological interest of AAO in flavor production is extended by its potential in production of chiral compounds taking advantage from the above-described stereoselectivity.

A Synthesis of 3,5-Disubstituted Phenols

Robust and scalable syntheses of some synthetically useful 3,5-disubstituted phenols are presented. The process involves the selective displacement of a halogen by nucleophilic aromatic substitution using a preformed mixture of potassium tert-butoxide and p-methoxybenzyl alcohol (PMB−OH), followed by deprotection of the PMB ether with acid in the presence of 1,3-dimethoxybenzene. These processes have been demonstrated on kilogram scale, providing crystalline phenols in good yield and high purity.

Liquid-Phase Oxidation of Some Aromatic Aldehydes, Hydrocarbons, and Alcohols by Cerium(IV) Catalyzed by Iridium(III) in Acidic Medium

Addition of traces of iridium(III) chloride with cerium(IV) sulfate (catalyst–substrate ratio (1:2994 to 1:10,000) in traditional water-bath heating resulted in the oxidation of p-chlorobenzaldehyde, p-nitrobenzaldehyde, benzyl alcohol, p-methoxy benzyl alcohol, p-xylene, and p-nitrotoluene dissolved in acetic acid to give 77%, 90%, 21.7%, 88.6%, 86.2%, and 18% yields of the products, respectively, while catechol and resorcinol polymerized. Oxidation of aldehydes and alcohols resulted as usual in the corresponding acids and aldehydes, respectively, while p-xylene and p-nitrotoluene gave p-tolualdehyde and p-nitrobenzoic acid. Conditions were obtained for getting the highest yields under the experimental conditions.

Electrochemical Investigation of the Behavior of Solid-supported Bases in Aprotic Organic Solvents Using Anodic Oxidation of p-Methoxybenzyl Alcohol as a Model Reaction

Abstract The behavior of solid-supported bases in aprotic organic solvents was investigated by cyclic voltammetry as well as preparative electrolyses using anodic oxidation of p-methoxybenzyl alcohol as a model reaction.

Torsional vibrational levels combined with higher frequency modes of the jet-cooled p-methoxybenzyl alcohol in the S 1 excited state

Resonant two-photon ionization (R2PI) spectrum of p-methoxybenzyl alcohol prepared in the supersonic jet has been obtained. Long-progression bands associated with torsional mode of the CH 2OH moiety with respect to the rest of the molecule in the S 1 state are observed in the wide spectral range of 35,500–37,500 cm −1. The torsional barrier height is found to decrease when the torsional mode is combined with other low-frequency bands at 84 ( ν 1=1) and 163 (ν 1=2) cm −1, indicating that this low-frequency mode is modestly coupled to the torsional mode. On the other hand, when the torsional mode is built on the higher-frequency band at 798 ( ν 2=1) and 1595 cm −1 ( ν 2=2), torsional frequencies are found to be little changed from those located at the origin. Ab initio calculation suggests that this relatively high-frequency mode may be associated with ring-deformation motions, which does not significantly modify the distance and angle between the CH 2OH moiety and aromatic ring. Rotational contour analysis suggests that the transition dipole moment is oriented along the molecular b-axis. The torsional progression bands in the excitation energies higher than ∼800 cm −1 are found to be much broader than those located at the origin, indicating that intramolecular vibrational redistribution (IVR) becomes quite efficient at such excitation energies.

Efficient Catalysis of Rare-Earth Metal Ions in Photoinduced Electron-Transfer Oxidation of Benzyl Alcohols by a Flavin Analogue

A flavin analogue (riboflavin-2‘,3‘,4‘,5‘-tetraacetate, Fl) forms the 1:1 and 1:2 complexes with rare-earth metal ions. The largest formation constants K1 and K2 for the 1:1 and 1:2 complexes between Fl and Sc3+ are determined as K1 = 3.1 × 104 M-1 and K2 = 1.4 × 103 M-1, respectively. The complexation of Fl with rare-earth metal ions results in blue shifts of the fluorescence maximum, shortening of the fluorescence lifetime, and more importantly the change in the lowest excited state from the n,π* triplet state of Fl to the π,π* singlet states of Fl−rare-earth metal ion complexes as indicated by the disappearance of the triplet−triplet (T−T) absorption spectrum of Fl by the complexation with metal ions. The strong complex formation between Fl and rare-earth metal ions enhances the oxidizing ability of the excited state of Fl as indicated by the significant acceleration in the fluorescence quenching rates of Fl−rare earth metal ion complexes via electron transfer from electron donors (e.g., alkylbenzenes) as compared to those of uncomplexed Fl. The one-electron reduction potential of the singlet excited state of the 1:2 complex between Fl and Sc3+, 1(Fl−2Sc3+)* (* denotes the excited state), is positively shifted by 780 mV as compared to 1Fl*. Such a remarkable enhancement of the redox reactivity of 1(Fl−2Sc3+)* as compared to that of 1Fl* makes it possible to oxidize efficiently p-chlorobenzyl alcohol to p-chlorobenzaldehyde by 1(Fl−2Sc3+)*, although no photooxidation of p-chlorobenzyl alcohol by Fl occurred in deaerated MeCN. The quantum yield for the photooxidation of p-chlorobenzyl alcohol by Fl−2Sc3+ is the largest among various Fl−metal ion complexes. A comparison of the observed rate constant derived from the dependence of the quantum yield on the concentration of p-chlorobenzyl alcohol with the fluorescence quenching rate constant by electron transfer from the alcohol and the direct detection of radical intermediates reveal that the photooxidation proceeds via electron transfer from p-chlorobenzyl alcohol to 1(Fl−2Sc3+)*. Under an atmospheric pressure of oxygen, the photooxidation of p-methoxybenzyl alcohol by oxygen proceeds efficiently in the presence of Fl−Lu3+ which acts as an efficient photocatalyst. No photodegradation was observed in the case of the Fl−Lu3+ complex, whereas the facile photodegradation of Fl−Mg2+ has precluded the efficient photocatalytic oxidation of the alcohol by oxygen.

An Efficient Method for the p-Methoxybenzylation of Hydroxy Groups with 2-(4-Methoxybenzyloxy)-3-nitropyridine

Abstract 2-(4-Methoxybenzyloxy)-3-nitropyridine (PMBONPy), easily prepared from 2-chloro-3-nitropyridine and p-methoxybenzyl (PMB) alcohol, reacts with various types of hydroxy groups in the presence of a catalytic amount of trimethylsilyl triflate (Me3SiOTf) to give the corresponding PMB ethers in high yields under mild conditions.

Asymmetric synthesis of quaternary centers. Total synthesis of (-)-malyngolide.

[structure] The deracemization of 3-nonyl-3,4-epoxybut-1-ene with Pd(0) in the presence of chiral ligands using p-methoxybenzyl alcohol as a nucleophile proceeds regio- and enantioselectively to form the monoprotected vinylglycidol in 99% ee. This chiral building block was converted in seven steps to (-)-malyngolide, an antibiotic showing significant activity against Mycobacterium smegmatis and Streptococcus pyogenes. An interesting aspect involves controlling the diastereoselectivity of protonation of an enolate via a distal hydroxyl group.