Carbonyl Components Research Articles

New Methods and Strategies in the Synthesis of Terpenoid Natural Products.

Indoloterpenoids of the paxilline type belong to a large family of secondary metabolites that exhibit unique molecular architectures and a diverse set of biological activities. More than 100 congeners identified to date share a common structural motif that contains an indole moiety fused to a rearranged diterpenoid fragment. The representative physiological and cellular effects attributed to this family of natural products include neurological and insecticidal activities, modulation of lipid balance, and inhibition of mitosis. The uniting polycyclic motif combined with the diversity of individual structural features of paxilline indoloterpenoids and the broad scope of their biological activities have fascinated organic chemists for the past four decades and have led to the development of numerous syntheses. In this Account, we describe our contributions to this field and how they in turn shape new directions that are developing in our laboratory.We begin with the discussion of our strategy for the synthesis of the shared indoloterpenoid core. To address stereochemical challenges encountered in earlier reports, we planned to leverage a suitably substituted cyclopentanone in a polycyclization to form the desired trans-decalin motif. This polycyclization relied on a radical-polar crossover cascade initiated by hydrogen atom transfer. The original process exhibited poor diastereoselectivity, but we discovered an efficient solution to this problem that took advantage of intramolecular tethering effects, culminating in short synthesis of emindole SB. During these studies, we also identified indium-mediated alkenylation of silyl enol ethers with alkynes as a suitable method for the synthesis of highly substituted β,γ-unsaturated ketones that was critical to achieving brevity of our route. We subsequently developed a catalytic version of this transformation that allowed for a formal bimolecular ene reaction that exhibited unusual and potentially useful selectivity in construction of quaternary centers.To test the scope and limitations of our approach to paxilline indoloterpenoids and identify potential improvements, we developed a synthesis of the more complex congener nodulisporic acid C. The convergent assembly of this natural product was enabled by identification of new elements of stereocontrol in the radical-polar crossover polycyclization en route to the polycyclic terpenoid motif and development of a highly diastereoselective enyne cycloisomerization to access the indenopyran motif and a ketone arylation protocol to unite the two complex fragments.In subsequent studies, we expanded the radical-polar crossover cascade underlying our approach to paxilline indoloterpenoids to a bimolecular setting, which allowed for annulation of two unsaturated carbonyl components to produce functionalized cyclohexanes. This transformation is particularly well suited for installation of fully substituted carbons and can be complementary to the venerable Diels-Alder reaction. The utility of the new annulation was tested in the synthesis of forskolin, allowing for rapid construction of the complex polycyclic motif in this densely functionalized labdane diterpenoid.Over the past five years, our initial forays into the synthesis of paxilline indoloterpenoids have grown into a program that incorporates development of new synthetic methods and pursues artificial assembly of terpenoid natural products from several different families. We are encouraged by the increasing diversity of structural motifs made accessible by application of this chemistry and continue to discover new aspects of the underlying reactivity.

Synthesis and herbicidal and fungistatic evaluation of Passerini adducts bearing phenoxyacetic moieties

A new idea for the modification of a carboxylic group in phenoxyacetic herbicides is proposed. Common herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA), and their chalcogen analogs (arylthio and arylselenyl fragments instead of a phenoxy one) were used as carboxylic components in the tricomponent Passerini reaction. Cyclohexyl isocyanide and 4-isocyano-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO-NC) were used as isocyanides. Acetone, acetaldehyde and formaldehyde were used as carbonyl components. Passerini adducts 4a–4L were obtained in yields of 32–59%. The structures of the Passerini adducts were determined using spectroscopic methods: MS, HR MS, 1H NMR, 13C NMR, 77Se NMR (if appropriate) and IR spectra (MS, HR MS, IR for the nitroxides 4k and 4L). The herbicidal activity of the Passerini adducts synthesized (4a–4L) was tested against ten weed species (at 2 kg/ha using 2,4-D and MCPA as a control). 100% herbicidal post-emergent activity was reported for 4i, 4j, 4k, 4L [a weed black mustard (Brassica nigra)], for 4k, 4L [weeds pale smartweed (Polygonum lapathifolium) and fathen (Chenopodium album)], as well as for 4k (weeds common poppy (Papaver rhoeas) and gallant soldier (Galinsoga parviflora)). The fungistatic activity of the Passerini adducts synthesized (4a–4L) was tested against six phytopathogenic fungi species (at 200 mg/L and procymidone as a control). The tested compounds showed a weak activity (% of inhibition) against: Alternaria alternata: 4g (47), 4i (26), 4j (26), 4k (50), Botrytis cinerea 4g (38), Fusarium culmorum 4g (44), Phytophthora cactorum 4i (35), 4j (35), 4k (30), Rhizoctonia solani 4g (30), 4i (24), Phytophthora infestans 4g (29), 4i (34), 4j (28), 4k (46).

Aminomethylated Hydroxinaphthalenes: Synthesis and Application

The analysis of the literature is carried out and the results of the synthetic approaches to the aminomethylation of hydroxy derivatives of naphthalenes developed over the past 20 years are presented. Most of the described aminomethylation processes proceed as Mannich aminomethylation or, as a special case of a similar condensation --- aminobenzylation according to Betti. The results of all studies are grouped according to the nature of the amine used in the synthesis: primary, secondary, tertiary. Most of the examples were considered for 2-naphthol, however, as the analysis of literature data shows, similar methods are applicable to 1-naphthol and dihydroxynaphthalenes with different positions of OH groups in the ring --- often only the yields of the target product differ. Both the classical methods for the preparation of Mannich and Betti bases using the carbonyl component (formaldehyde, benzaldehyde and its derivatives, respectively) and special cases of synthesis, in which condensation is carried out by means of halogen derivatives, substituted azacrown ethers, etc., are presented. Particular attention is paid to the use of various catalysts and activators, allowing to significantly simplify the synthetic procedures and increase the yields of target compounds. The main fields of application of aminomethylated derivatives of hydroxynaphthalenes are presented

Synthesis of novel 3-(1,2,4-oxadiazol-5-yl)thiophen-2-amine derivatives via gewald reaction

Novel substituted 3-(1,2,4-oxadiazol-5-yl)thiophen-2-amines were obtained by the multicomponent Gewald reaction of an activated nitrile with 1,2,4-oxadiazole moiety, a carbonyl component and elemental sulphur in the presence of morpholine as a catalyst. Keywords : 2-aminothiophenes, 1,2,4-oxadiazole, Gewald reaction, multicomponent reaction.

Pyrolysis Kinetic Study and Reaction Mechanism of Epoxy Glass Fiber Reinforced Plastic by Thermogravimetric Analyzer (TG) and TG-FTIR (Fourier-Transform Infrared) Techniques.

TG–FTIR combined technology was used to study the degradation process and gas phase products of epoxy glass fiber reinforced plastic (glass fiber reinforced plastic) under the atmospheres of high purity nitrogen. The pyrolysis characteristics of epoxy glass fiber reinforced plastic were measured under different heating rates (5, 10, 15, 20 °C min−1) from 25 to 1000 °C. The thermogravimetric analyzer (TG) and differential thermogravimetric analyzer (DTG) curves show that the initial temperature, terminal temperature, and temperature of maximum weight loss rate in the pyrolysis reaction phase all move towards high temperature, as the heating rate increases. Epoxy glass fiber reinforced plastic has two stages of thermal weightlessness. The temperature range of the first stage of weight loss is 290–460 °C. The second stage is 460–1000 °C. The above two weight loss stages are caused by pyrolysis of the epoxy resin matrix, and the glass fiber will not decompose. The dynamic parameters of glass fiber reinforced plastic were obtained through the Kissinger-Akahira-Sunose (KAS), Flynn–Wall-Ozawa (FWO) and advanced Vyazovkin methods in model-free and the Coats–Redfern (CR) method in model fitting. FTIR spectrum result shows that the main components of the product gas are CO2, H2O, carbonyl components, and aromatic components during its pyrolysis.

Isonitrile-Based Multicomponent Synthesis of β-Amino Boronic Acids as β-Lactamase Inhibitors.

The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers–three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected β-aminoboronic acids. The corresponding free β-aminoboronic acids, quantitatively recovered through basic mild deprotection, were found to be quite stable and were fully characterized, including by 11B-NMR spectroscopy. Single-crystal X-ray diffraction analysis, applied both to a MIDA-protected and a free β-aminoboronic acid derivative, provided evidence for different conformations in the solid-state. Finally, the antimicrobial activities of selected compounds were evaluated by measuring their minimal inhibitory concentration (MIC) values, and the binding mode of the most promising derivative on OXA-23 class D β-lactamase was predicted by a molecular modeling study.

Tertiary Amine Synthesis by Radical Carbonyl Alkylative Amination

Highly efficient access to structurally diverse branched tertiary amines is a long-standing challenge in synthetic chemistry. In a recent paper published in Nature, Gaunt and co-workers disclose a practical strategy for the construction of synthetically intractable tertiary amines through visible-light-mediated radical carbonyl alkylative amination of aldehydes, amines, and alkyl halides.

Functionalized heterocycle-appended porphyrins: catalysis matters.

The scope and limitations of the condensation of labile 2,3-diaminoporphyrin derivatives with aromatic aldehydes to provide functionalized imidazole- and pyrazine-appended porphyrins were investigated in detail. The presence of an acidic catalyst in the reaction was found to be a tool that allows the reaction path to be switched. The influence of the electronic origin of the substituents in the carbonyl components of the condensation on the yields and selectivity of the reaction was revealed. Metal-promoted cross-coupling transformations were found to be convenient for the further targeted construction of functional derivatives based on the prepared bromo-substituted pyrazinoporphyrins. Overall, these strategies provide a versatile technique for the elaboration of a variety of functionalized heterocycle-appended porphyrins for further application in the development of hybrid materials.

Effect of the traditional koumiss yeast produced in Turkey on some properties and carbonyl components of koumiss

Effect of the traditional koumiss yeast produced in Turkey on some properties and carbonyl components of koumiss

Reduction of Pb(II) Ion in Soybean Seeds (Glycine max) Using Corncob Liquid Smoke

This research aims to study the ability of corncob liquid smoke for reduce of Pb(II) Ion in soybean seeds and the influence of its constituent compounds in reducing of Pb content in soybean seeds. The liquid smoke was obtained from corncob via pyrolysis, precipitation and two-time distillation. The process of reducing Pb content in soybean seeds is by soaking soybean seeds in liquid smoke with variations in the concentration of liquid smoke (0; 12.5; 25; 50 and 100%). Results show that the phenol, carbonyl and acid total content of corncob liquid smoke were 1.22%; 5.65%; and 9.60%; respectively. The corncob liquid smoke with concentration of 100% is able to reduce Pb content in soybean seeds by 48.93%. The components of phenol, carbonyl and acid in liquid smoke reduce after the chelation process. This shows that phenol, carbonyl and acid components influence the reduce Pb content in soybean seeds.

Investigation into the Oxidative Aging of Asphalt Binders

Oxidative aging is caused by oxygen diffusion into the binder when an asphalt pavement is exposed to the atmosphere. Aging can lead to increased susceptibility to pavement damage (i.e., raveling, cracking, and moisture damage). Investigation of the aging mechanism advances the understanding of these pavement distresses, and prediction of the aging progress improves structural design and prediction of pavement performance. Previous studies have proposed a dual-rate aging model that divides the aging progress into a short, fast-rate phase and a long constant phase. This paper further investigates the constant rate aging phase of unmodified, polymer modified, and asphalt rubber binders. The chemical composition (carbonyl, sulfoxide, ether, and ester) and the rheological properties (shear modulus and viscosity) changes were tracked to analyze the binder aging mechanism. As expected, the carbonyl component was found to consistently increase with aging time. The widely used aging model with kinetics parameters estimated from the accelerated laboratory test predicted the field-aging progress reasonably well. A linear correlation between the logarithm of viscosity change and the carbonyl change was found to be valid for a wide range of loading temperatures and frequencies. Furthermore, the slope of this linear correlation was found to be in perfect linear correlation with the loading frequency. These findings point to a generic framework for studying aging and its effect on asphalt binders, as well as asphalt concrete mixes.

The studies on chemoselective promiscuous activity of hydrolases on acylals transformations

Chemoselective, mild and convenient protocol for the hydrolysis of the synthetically relevant acylals via promiscuous enzyme-catalyzed hydrolysis has been developed. It has been shown that promiscuous activity of the used hydrolases dominates their native activity related with carboxylic esters hydrolysis. The main advantage of the present methodology is that it can be conducted under neutral conditions at room temperature. Moreover, complete deprotection of acylals takes place within 10–20 min. Developed protocol can be used with compounds having a variety of hydrolytic labile groups since the cleavage is proceeded under neutral conditions and occurs exclusively on acylal moiety. Further this protocol was extended by the tandem Passerini multicomponent reaction leading to the α-acetoxy amides using acylals as the surrogates of the carbonyl components to P-MCR.

Introducing the Petasis Reaction for Late-Stage Multicomponent Diversification, Labeling, and Stapling of Peptides.

For the first time, the Petasis (borono-Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid-phase derivatization of peptides at the N-terminus, Lys, and Nϵ -MeLys side-chains by an on-resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity-generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking Nϵ -MeLys or Orn side-chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.

Introducing the Petasis Reaction for Late‐Stage Multicomponent Diversification, Labeling, and Stapling of Peptides

AbstractFor the first time, the Petasis (borono‐Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid‐phase derivatization of peptides at the N‐terminus, Lys, and Nϵ‐MeLys side‐chains by an on‐resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity‐generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking Nϵ‐MeLys or Orn side‐chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.

A Rapid, Univariate FT-NIR Procedure to Determine Moisture Concentration in Olive Oil.

We recently observed that the weak near-infrared (NIR) band near 5260 cm-1 was relatively more intense for extra virgin olive oil (EVOO) than for refined olive oil (ROO). We also observed that its intensity was diminished upon heating and erroneously presumed that it may be attributed to volatile carbonyl components in EVOO. In the present study we demonstrate for the first time that this band is primarily attributed to a water O-H combination band. To accurately determine the intensity of this weak band, observed on a shifted and sloping baseline, we measured the peak-to-peak (p-p) height of its first derivative. An exponential calibration curve for p-p height versus gravimetrically-determined concentration of spiked water was satisfactorily generated. The calibration curve was first evaluated by using independent sets of gravimetrically prepared test samples. Subsequently, it was used to determine the moisture content, a quality parameter, for a limited set of authenticated reference olive oils whose quality and purity were confirmed by official methods. These concentrations, 0.098-0.12% H2O (w/w) for EVOO, 0.022-0.030% H2O (w/w) for ROO, and 0.028-0.054% H2O (w/w) for pomace olive oil (POO), were consistent with those reported in the literature. For 88 commercial products investigated, the moisture levels fell in the range from 0.026% to 0.13% (w/w). The correlation between moisture content and other olive oil quality parameters has been reported in the literature and has yet to be further investigated.

Multicomponent Approach to a Library of N-Substituted γ-Lactams.

The γ-lactam motif is often found in naturally occurring compounds with diverse biological activities. We prepared a 28-member library of N-substituted γ-lactams following a single-pot, three-component Ugi reaction comprising bifunctional building block, l-glutamic acid methyl ester. The reaction tolerates structurally diverse carbonyl and isocyanide components providing a robust access to functionalized γ-lactams. Antimicrobial susceptibility testing, including agar well diffusion assay, serial microdilution broth assay, and antibiofilm activity testing, identified a potent compound with antibiofilm activity against Staphylococcus aureus ATCC 6538.

Synthesis of pyrrolizidines and indolizidines by multicomponent 1,3-dipolar cycloaddition of azomethine ylides

AbstractDifferent multicomponent 1,3-dipolar cycloadditions (1,3-DC) of cyclic α-amino acid derivatives with aldehydes and dipolarophiles have been described as efficient and simple methodologies for the synthesis of the pyrrolidine unit of pyrrolizidines and indolizidines. When free cyclic α-amino acids are used, a thermal promoted decarboxylative process generatesin situthe corresponding non-stabilized azomethine ylides, which afforded the corresponding pyrrolizidines and indolizidines with a hydrogen in the bicyclic units. This methodology has been employed to the synthesis of complex systems including spiro derivatives when ketones are used as carbonyl component. In addition, working with cyclic α-amino acid derived esters, the three-component 1,3-DC takes place under milder reaction conditions giving the corresponding pyrrolizidines and indolizidines with an alkoxycarbonyl group in the bridge adjacent carbon to the nitrogen. This methodology can be carried out by a double consecutive or stepwise 1,3-DC to provide pyrrolizidines via the precursor prolinates. The conformation of the azomethine ylide controls the endo/exo diastereoselectivity of the 1,3-DC.

On the Mechanism of Trimethylphosphine-Mediated Reductive Dimerization of Ketones.

High-level single-reference calculations reveal that trimethylphosphine-mediated reductive dimerization of properly substituted (e.g., CF3) ketones proceeds via initial formation of an oxaphosphirane intermediate, with the oxygen atom occupying an equatorial position at phosphorus. In the "oxirane route", this oxaphosphirane intermediate loses a trimethylphosphine oxide unit, thus behaving as a carbene transfer agent toward a second carbonyl molecule and giving rise to a carbonyl ylide that cyclizates to the corresponding oxirane. This in turn transfers the carbene unit to a second phosphine molecule, with loss of acetone, affording a phosphorane. The latter undergoes typical Wittig reaction to the final homocoupling product through the oxaphosphetane intermediate. The alternative direct conversion of oxaphosphirane into phosphorane constitutes the lowest energy path as it skips the highest barrier oxirane → phosphorane conversion. The oxirane route is favored by the use of polar solvents and electron deficient carbonyl components. The lowest barrier most exergonic process from oxaphosphirane is the pericyclic cycloaddition of the acetone C═O bond along the endocyclic P-C bond, furnishing the stable 1,3,2-dioxaphospholane product.

The effect of microbial transglutaminase on probiotic fermented milk produced using a mixture of bovine milk and soy drink

In this study, the effects of microbial transglutaminase (m‐TGs) enzymes on the physicochemical, microbial and sensorial properties of probiotic fermented milk produced using a mixture of bovine milk and soy drink were investigated. Probiotic fermented milk samples were prepared by 3:1 v/v bovine milk, 0.002 w/v soy drink and 0, 0.5, 1, 1.5 U m‐TGs per gram of milk protein. The starter culture used was ABT‐2 1000 I (a mixture of Lactobacillus acidophilus LA‐5, Bifidobacterium animalis subsp. lactis BB‐12 and Streptococcus thermophilus). Viscosity and hardness values increased with increased transglutaminase ratio, whereas syneresis values decreased. All samples had an apparently acceptable number of probiotic bacteria over the storage period. While the minimum and maximum percentage ratios of alcohol components and carbonyl components in total volatile aromatic components of fermented milk samples are 24.75–30.70% (v/v) and 65.66–71.96% (v/v) during storage time, the minimum and maximum percentage ratios of organic acids and esters are 0.56–2.54% (v/v) and 0.73–1.57% (v/v).

Low-Temperature Electrochemical Upgrading of Bio-oils Using Polymer Electrolyte Membranes

While bio-oil-derived fuels hold much promise as a replacement for petroleum, transformation of the highly oxygenated mixture has proven challenging. In particular, bio-oils are reactive and difficult to upgrade through catalytic pyrolysis. To reach a stabilized product capable of deep deoxygenation at elevated pressure and temperature, conversion or separation of reactive groups is required. This paper describes an electrochemical process for stabilization and upgrading of bio-oils prior to hydrotreating at high pressure and temperature. This electrolytic process uses a three-compartment cell designed to hydrogenate reactive carbonyl components while separating small acid molecules, such as acetic and formic acids, which act as catalysts for condensation reactions and consume hydrogen gas to produce low-value gases in hydrotreating. To avoid conductivity issues, electrodes are appended to anion- and cation-exchange membranes. The cell was tested using a mixed acetic acid and formic acid surrogate fed to ...