Alcohol Derivatives Research Articles

A three-component reaction of arynes, sodium sulfinates, and aldehydes toward 2-sulfonyl benzyl alcohol derivatives.

A novel three-component reaction of arynes, sodium sulfinates, and aldehydes under mild reaction conditions is described. This transformation provides a direct synthetic approach to 2-sulfonyl benzyl alcohol derivatives, which could be rapidly converted to diverse arylsulfur compounds via the transformation of the corresponding hydroxyl groups. Various aryne precursors, sodium arenesulfinates, and aromatic aldehydes can be effectively converted to the desired products in 40-84% yields (29 examples).

Development of Nickel-Catalyzed Cross-Coupling of Alcohol Derivatives to Construct Carbon-Carbon Bonds

Development of Nickel-Catalyzed Cross-Coupling of Alcohol Derivatives to Construct Carbon-Carbon Bonds

Nonpeptide small molecules with a ten-membered macrolactam or a morpholine motif from the insect American cockroach and their antiangiogenic activity

(±)-Periplactam A (1), a rare ten-membered macrolactam composed of lignan and putrescine, (±)-periplanol E (2), a dimeric phenethyl alcohol derivative formed via morpholine, and periplactams B (3) and C (4) were isolated from American cockroach.

Selective oxidation of benzyl alcohols with molecular oxygen as the oxidant using Ag-Cu catalysts supported on polyoxometalates

We report an efficient process for the oxidation of benzyl alcohols using molecular oxygen as the oxidant catalyzed by Ag-Cu catalysts supported on polyoxometalates (Ag-Cu/POM). The Ag-Cu/POM catalyst was prepared by galvanic displacement in the presence of polyvinyl pyrrolidone and polyethylene glycol. The catalysts were characterized using Fourier transform infrared spectroscopy (FTIR), ultraviolet–visible spectroscopy (UV–Vis), powder X-ray diffraction (PXRD), X-ray fluorescence (XRF), Brunauer-Emmett-Teller (BET) surface analysis, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS) and thermogravimetric analysis (TGA). The oxidation reaction was carried out using a Schlenk– line setup, under ambient atmospheric pressure. Reaction products were identified by GC–MS and quantified with GC using an internal standard method. The Ag-Cu/POM catalyst gave close to 100% benzyl alcohol conversion in 5 h with >99% selectivity to benzaldehyde. When tested on various benzyl alcohol derivatives the Ag-Cu catalysts showed good conversions and >99% selectivity to the corresponding aldehydes. The Ag-Cu catalysts supported on the POM are highly stable, and don’t show tendency to leach or deactivate. The catalysts are heterogeneous in nature and easy to recover after reactions, and could be reused at least 5 times without significant loss in activity and selectivity.

Hydrosilylation and Mukaiyama aldol-type reaction of quinolines and hydrosilylation of imines catalyzed by a mesoionic carbene-stabilized borenium ion.

Aldimines and ketimines containing electron-donating and electron-withdrawing groups can be hydrosilylated with borenium catalysts at as low as 1 mol% catalyst loading at room temperature, providing the corresponding secondary amines in excellent yields. Reactions with 2-phenylquinoline gave the 1,4-hydrosilylquinoline product selectively which can be further functionalized in a one-pot synthesis to give unique γ-amino alcohol derivatives. Control experiments suggest that the borenium ion catalyzes both the hydrosilylation and subsequent addition to the aldehyde.

Analysis of the ethyl stearate properties as a new alternative to cocoa butter

The object of research is the product of modification of fats, in particular derivatives of fatty acids and monohydric alcohols, namely ethyl stearate. One of the biggest challenges for the confectionery industry is the use of modified fats that fully meet food safety requirements. Existing modified fats, used in confectionery, mainly contain saturated fatty acids with carbon atoms of 16 or less, identified by the World Health Organization (WHO) as harmful to the human body. Without the presence of a significant amount of trans fatty acids, it is difficult to obtain inexpensive modified fats that have high hardness at a low melting point. The reduction of trans fatty acid isomers in modified fats is a worldwide problem. In addition, the presence of glycerol in the composition of trihydric alcohol fats can promote the formation of glycidol esters. In turn, glycidol esters are known to contribute to the development of cancer. It is practically impossible to obtain triacylglycerols, which contain only stearic acid among the saturated fatty acids. This is a significant obstacle to the formation of a rational fatty acid composition in terms of the content of saturated acids.It is proposed to solve certain problems by means of a new technology for modifying fats, namely by replacing in the composition of fats – acylglycerol of the alkyl group. As an alternative to cocoa butter in confectionery products, according to the author’s data, stearic acid ethyl ester can be used. A complex of studies has determined that ethyl stearate, by its physical and chemical properties, namely: melting point, mass fraction of solid ethers and solubility in acylglycerols in any ratio, is a full-fledged alternative to cocoa butter.The use of new modified fats, in particular ethyl stearate in the composition of confectionery, will allow to exclude saturated fatty acids from the diet; according to WHO, they contribute to an increase in low density lipoproteins in human blood.

Non-invasive monitoring of the kinetic infiltration and therapeutic efficacy of nanoparticle-labeled chimeric antigen receptor T cells in glioblastoma via 7.0-Tesla magnetic resonance imaging

Background aimsChimeric antigen receptor (CAR) T-cell therapy is a promising treatment strategy in solid tumors. In vivo cell tracking techniques can help us better understand the infiltration, persistence and therapeutic efficacy of CAR T cells. In this field, magnetic resonance imaging (MRI) can achieve high-resolution images of cells by using cellular imaging probes. MRI can also provide various biological information on solid tumors. MethodsThe authors adopted the amino alcohol derivatives of glucose-coated nanoparticles, ultra-small superparamagnetic particles of iron oxide (USPIOs), to label CAR T cells for non-invasive monitoring of kinetic infiltration and persistence in glioblastoma (GBM). The specific targeting CARs included anti-human epidermal growth factor receptor variant III and IL13 receptor subunit alpha 2 CARs. ResultsWhen using an appropriate concentration, USPIO labeling exerted no negative effects on the biological characteristics and killing efficiency of CAR T cells. Increasing hypointensity signals could be detected in GBM models by susceptibility-weighted imaging MRI ranging from 3 days to 14 days following the injection of USPIO-labeled CAR T cells. In addition, nanoparticles and CAR T cells were found on consecutive histopathological sections. Moreover, diffusion and perfusion MRI revealed significantly increased water diffusion and decreased vascular permeability on day 3 after treatment, which was simultaneously accompanied by a significant decrease in tumor cell proliferation and increase in intercellular tight junction on immunostaining sections. ConclusionThese results establish an effective imaging technique that can track CAR T cells in GBM models and validate their early therapeutic effects, which may guide the evaluation of CAR T-cell therapies in solid tumors.

Dual Catalytic Strategy for Forging sp2-sp3 and sp3-sp3 Architectures via β-Scission of Aliphatic Alcohol Derivatives.

A dual platform for forging sp2-sp3 and sp3-sp3 carbon bonds via catalytic β-scission of aliphatic alcohol derivatives with both aryl and alkyl halides is disclosed. This protocol is distinguished by its wide substrate scope and broad applicability, even in the context of late-stage functionalization.

Harnessing C-O Bonds in Stereoselective Cross-Coupling and Cross-Electrophile Coupling Reactions.

Herein, we discuss our laboratory's research in the activation of alcohol derivatives in cross-coupling and cross-electrophile coupling reactions. Our developed methods enable the use of secondary alcohols to afford tertiary stereogenic centers, which we applied to the synthesis of pharmaceutically relevant compounds and substructures. We first discuss the synthesis of bioactive compounds via stereospecific Kumada cross-coupling reactions, followed by a discussion on the development of our stereoselective cross-electrophile coupling reaction to synthesize cyclopropanes.

Thiophenols as Protic Nucleophilic Triggers in Aryne Three-Component Coupling.

The synthetic potential of thiophenols as a protic nucleophilic trigger in the transition-metal-free and Grignard-reagent-free three-component coupling involving arynes is demonstrated. Employing aldehydes as the third component, the reaction allowed the mild and broad scope synthesis of 2-arylthio benzyl alcohol derivatives in good yields. Moreover, selenophenol could be used as the nucleophilic trigger, and activated ketones could be used as the third component in this reaction.

Transition‐Metal‐Catalyzed Propargylic Substitution of Propargylic Alcohol Derivatives Bearing an Internal Alkyne Group

AbstractThe development of the transition‐metal‐catalyzed propargylic substitution of propargylic alcohol derivatives is one of the active research subjects in organic synthesis. In this minireview, we summarize the catalytic propargylic substitution of propargylic alcohol derivatives bearing an internal alkyne group using a transition metal as the catalyst. Although the asymmetric propargylic substitution of the substrate class still underdeveloped, some transition metal catalyses using nickel, palladium, and copper, and the cooperative catalysis enabled the challenging transformation. A various types of transition‐metal catalysts are known to promote the non‐asymmetric propargylic substitution of the internal alkyne‐substituted propargylic alcohol derivatives via a propargylic cation intermediate, realizing the carbon‐carbon and carbon‐heteroatom bond formation at the propargylic position.

Activation of carbonic anhydrases from human brain by amino alcohol oxime ethers: towards human carbonic anhydrase VII selective activators

The synthesis and carbonic anhydrase (CA; EC 4.2.1.1) activating effects of a series of oxime ether-based amino alcohols towards four human (h) CA isoforms expressed in human brain, hCA I, II, IV and VII, are described. Most investigated amino alcohol derivatives induced a consistent activation of the tested CAs, with KAs spanning from a low micromolar to a medium nanomolar range. Specifically, hCA II and VII, putative main CA targets when central nervous system (CNS) diseases are concerned, were most efficiently activated by these oxime ether derivatives. Furthermore, a multitude of selective hCA VII activators were identified. As hCA VII is one of the key isoforms involved in brain metabolism and other brain functions, the identified potent and selective hCA VII activators may be considered of interest for investigations of various therapeutic applications or as lead compounds in search of even more potent and selective CA activators.

Phytochemical constituents of leaves and twigs of Elaeagnus umbellata

A phytochemical study of the leaves and twigs of Elaeagnus umbellata Thunb. has led to the isolation and identification of 12 compounds, including two flavonoid coumaroyl glycosides (1 and 2), two simple phenolic compounds (3 and 4), one coniferyl alcohol derivative (5), one monoterpene (6), two pairs of enantiomeric neolignans (7a/7b and 8a/8b), and a pair of enantiomeric sesquineolignans (9a/9b). The structures of these compounds were elucidated through the analysis of their MS, ECD, and 1D/2D NMR spectra as well as comparison with previously reported data. This is the first time that 1 and 2 have been isolated from this species, and the first time that 5, 6, 7a, 7b, 8a, 8b, 9a, and 9b have been identified in the Elaeagnaceae family.

Gold‐catalyzed Cyclization of Non‐conjugated Ynone‐oxime Derivatives: Incorporation of Solvent Molecule

AbstractAuııı‐promoted cyclization reaction of ynone‐oxime derivatives furnished 4H‐1,2‐oxazine ring under mild reaction conditions. When an alcohol is present in the reaction media, it was attached to the oxazine ring by the second activation of cyclic intermediate with a gold catalyst. Cholesterol, propargyl alcohol, phenol, and some of the different alcohol derivatives with alkyl chain were bonded to the oxazine ring in good yields. While amine derivatives did not attach to the ring under optimized reaction conditions, the molecule with the thiol group deactivated the gold catalyst under the same reaction conditions and did not give any cyclic products. With the obtained cyclization protocol, 11 unknown oxazine derivatives were synthesized and characterized. The proposed cyclization mechanism was drawn according to the two independent control experiments, DFT optimization, and NBO charges.

Effective and selective aerobic oxidation of primary and secondary alcohols using CoFe2O4@HT@Imine‐CuII and TEMPO in the air atmosphere

In this study, we present a versatile and easy procedure for modifying a cobalt ferrite nanoparticle step by step. A new nanocatalyst was prepared via CuII immobilized onto CoFe2O4@HT@Imine. The catalyst was fully characterized by Fourier‐transform infrared (FT‐IR), energy‐dispersive X‐ray spectroscopy (EDX), field emission scanning electron microscopy (FE‐SEM), X‐ray diffraction (XRD), and vibrating sample magnetometer (VSM) analyses. The current procedure as a green protocol offers benefits including a simple operational method, an excellent yield of products, mild reaction conditions, minimum chemical wastes, and short reaction times. Without any significant reduction in the catalytic performance, up to five recyclability cycles of the catalyst were obtained. The optimization results suggest that the best condition in the oxidation of benzyl alcohol derivatives is 0.003 g of the CoFe2O4@HT@Imine‐CuII catalyst, TEMPO, at 70°C under solvent‐free condition and air.

Identification of the metabolites of piperine via hepatocyte incubation and liquid chromatography combined with diode-array detection and high-resolution mass spectrometry.

Piperine, an alkaloid isolated from Piper nigrum L., has been demonstrated to have many pharmacological effects and several health benefits. The aim of this work was to study the metabolic profiles of piperine in mouse, rat, dog and human hepatocytes. The biotransformation was carried out by incubating piperine with hepatocytes at 37°C. After incubation for 2 h, the samples were pretreated and analyzed using liquid chromatography combined with diode-array detection and high-resolution mass spectrometry (LC/DAD-HRMS). The structures of the metabolites were assigned through a comparison of their accurate masses and product ions with those of the parent compound. A total of 20 metabolites were detected, and the structures were proposed. Piperine was metabolized through the following pathways: (a) oxidation to form a catechol derivative, which further underwent methylation, glucuronidation, glutathione (GSH) conjugation, and hydroxylation followed by opening of the piperidine ring; (b) hydroxylation to form a carbinolamine intermediate followed by opening of the piperidine ring and the formation of alcohol and acid derivatives; and (c) hydroxylation to form stable hydroxylated metabolites. In mouse, the formation of the catechol derivative (M12) and hydroxylation (M11) were the major metabolic pathways; in rat, the formation of the catechol derivative (M12) and glucuronidation (M9) were the main pathways; and in dog and human, the formation of the catechol derivative (M12) was the predominant pathway. No human-specific metabolite was observed. This study provided some new information on the metabolic profiles of piperine, which should be of great importance in the study of the pharmacology and toxicity of this compound.

Molecular docking studies, drug-likeness and in-silico ADMET prediction of some novel β-Amino alcohol grafted 1,4,5-trisubstituted 1,2,3-triazoles derivatives as elevators of p53 protein levels

Malaria is a killer disease caused by Plasmodium falciparum and is responsible for over a million death annually. Chloroquine, quinine, pyrimethamine, proguanil, artemisinin, atovaquone, and mefloquine are different kinds of drugs employed to treat the disease, but due to increased drug resistance to these drugs, their use becomes less effective. Hence, the need for new antimalarial drugs with better activities and a new mechanism of action along different pathways against a new target. As well as the knowledge of their interactions, the drug-likeness of antimalarial drugs is necessary. Twenty-four derivatives of β-Amino alcohol grafted 1,4,5-trisubstituted 1,2,3-triazoles were docked against a p53 protein, as well as predicting their drug-likeness and ADMET properties. From the docking analysis, compound 10, {1-(1-benzyl-5-phenyl-1H-1,2,3-triazol-4-yl)-1-(4-bromophenyl)-2-((3,4-dimethylphenyl)amino)ethanol} was found to be the most stable compound with Re-rank docking score -100.295KJmol−1 against p53 protein. The “drug-likeness” and ADMET prediction performed nearly showed compliance with the Lipinski rule, and the compounds were found to have good absorption, distribution, metabolism, and excretion generally. The results of the study can be used for future optimization of derivatives of {1-(1-benzyl-5-phenyl-1H-1,2,3-triazol-4-yl)-1-(4-bromophenyl)-2-((3,4-dimethylphenyl)amino)ethanol}for better molecular interactions with p53 protein, and effective Plasmodium falciparum inhibition.

Enantioseparation of racemic amino alcohols using green micellar liquid chromatography and confirmation of absolute configuration with elution order

ABSTRACT Micellar liquid chromatographic method was developed for the enantioseparation of racemic amino alcohols. For that, diastereomeric derivatives of amino alcohols were prepared with activated ester of (S)-ketoprofen and separated on C18 column of RP-HPLC using the aqueous solution of surfactant (Brij-35 and SDS) as an alternative of the organic solvents. Also, chromatographic conditions were optimized by varying concentration of surfactant in aqueous solution, and by varying concentration and pH of the buffer. In addition, density functional theoretical calculations (DFT), validation [LOD (0.245 ng mL−1) and LOQ (0.735 ng mL−1)] and green-assessment score (82 score) were calculated for the developed method.

Mechanistic Insight into Concerted Proton-Electron Transfer of a Ru(IV)-Oxo Complex: A Possible Oxidative Asynchronicity.

We have thoroughly investigated the oxidation of benzyl alcohol (BA) derivatives by a RuIV(O) complex (RuIV(O)) in the absence or presence of Brønsted acids in order to elucidate the proton-coupled electron-transfer (PCET) mechanisms in C-H oxidation on the basis of a kinetic analysis. Oxidation of BA derivatives by RuIV(O) without acids proceeded through concerted proton-electron transfer (CPET) with a large kinetic isotope effect (KIE). In contrast, the oxidation of 3,4,5-trimethoxy-BA ((MeO)3-BA) by RuIV(O) was accelerated by the addition of acids, in which the KIE value reached 1.1 with TFA (550 mM), indicating an alteration of the PCET mechanism from CPET to stepwise electron transfer (ET) followed by proton transfer (PT). Although the oxidized products of BA derivatives were confirmed to be the corresponding benzaldehydes in the range of acid concentrations (0-550 mM), a one-electron-reduction potential of RuIV(O) was positively shifted with increases in the concentrations of acids. The elevated reduction potential of RuIV(O) strongly influenced the PCET mechanisms in the oxidation of (MeO)3-BA, changing the mechanism from CPET to ET/PT, as evidenced by the driving-force dependence of logarithms of reaction rate constants in light of the Marcus theory of ET. In addition, dependence of activation parameters on acid concentrations suggested that an oxidative asynchronous CPET, which is not an admixture of the CPET and ET/PT mechanisms, is probably operative in the boundary region (0 mM < [TFA] < 50 mM) involving a one-proton-interacted RuIV(O)···H+ as a dominant reactive species.

HFO‐1234yf as a CF3‐Building Block: Synthesis and Chemistry of CF3‐Ynones

Reaction of low cost, readily available 4th generation refrigerant gas 2,3,3,3‐tetrafluoropropene (HFO‐1234yf) with lithium diisopropylamide (LDA) leads to formation of lithium 3,3,3‐trifluoropropynide, addition of which to a range of aldehydes formed CF3‐alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess–Martin periodinane (DMP) to give substituted CF3‐ynones with minimal purification required. Michael‐type additions of alcohol and amine nucleophiles to CF3‐ynones are rapid and selective, affording a range of CF3‐enone ethers and enaminones in excellent yields with high stereoselectivity for the Z‐isomer. By analogous reactions with difunctional nucleophiles, a wide range of CF3‐substituted pharmaceutically relevant heterocyclic structures can be accessed, exemplified in the simple synthesis of the anti‐arthritis drug celecoxib from HFO‐1234yf in just three steps.