Radical reductions of alkyl halides bearing electron withdrawing groups with N-heterocyclic carbene boranes

1,3-Dimethylimidazol-2-ylidene borane and 2,4-dimethyl-1,2,4-triazol-3-ylidene borane are found to be useful reagents for the reduction of alkyl iodides and bromides bearing nearby electron withdrawing substituents. Signatures of radical chain reactions are seen in many cases, but ionic reductions may also be occurring with some substrates. The reagents are attractive because of their low molecular weight, their availability from inexpensive precursors, and their stability. Separation of the borane products from the target products is readily accomplished either with or without prior regeneration of the borane for later reuse. 2,4-Dimethyl-1,2,4-triazol-3-ylidene borane is versatile because both starting borane and its derived products can be removed by extraction with water.     

Antibacterial Natural Products in Medicinal Chemistry—Exodus or Revival?

To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti-infectives. Surprisingly, numerous "old" classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the "old fashioned" natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target-finding tools from biology (reversed genomics) is one option for their revival.     

Recent topics of the stereodivergent synthesis of natural products

A variety of natural products, a valuable source of drug lead compounds, coexist with their stereoisomers as congeners. For pursuing the structural elucidation and the structure–activity relationship study of natural products, it is needed to establish the streamlined synthetic route to supply natural products and their stereoisomers. Divergent pathway is one of the synthetic strategies to deliver more than one target compound. In this digest, selected examples of the stereodivergent approach toward the synthesis of natural products are described. Especially, this digest focuses on common synthetic intermediates and stereodiversification steps from the common intermediates to reach the target compounds.     

Biradical and zwitterionic cyclizations of oxy-substituted enyne-allenes

[see reaction]. Oxyanion substitution of enyne-allenes causes both Myers-Saito and Schmittel cyclizations to switch their product formation preferences from diradicals to polar, closed-shell singlets. The oxyanion stabilization is larger for the Schmittel products than the Myers-Saito products because the latter must sacrifice aromaticity to maximize interaction. The changing character of the different reaction paths is reflected in their activation energies.     

Quantitative determination of erythromycin and its hydrolysis products by cyclic voltammetry at the interface between water and 1,2-dichloroethane

An electrochemical method for quantifying erythromycin (Er) salts and their hydrolysis products is described. Cyclic voltammetry at the water/1,2-dichloroethane interface in a four-electrode system was used. A linear relationship between I_p and the erythromycin concentration was obtained up to the solubility limit of the antibiotic. The various hydrolysis products which can be obtained in acid or basic solutions were characterized by their respective transfer potentials. Similar hydrolysis products were observed for aged solutions of Er lactobionate.It is concluded that the proposed method is suitable for the quantification of Er and for distinguishing it from its hydrolysis products.     

Determination of Some Cephalosporins Using Derivative Spectrophotometry

Abstract

A rapid and simple method for the determination of cephalexin, cephalothin sodium and cephradin without prior separation from their alkali-induced degradation products is presented. By measuring the values of the first and second derivative spectra at certain wavelengths, the concentration of the intact drug can be calculated directly without interference of degradation products. The method was proved using synthetic mixtures of the intact drugs with their degradation products, and its suitability to monitor the stability of the drugs was demonstrated.     

Electrophilic natural products and their biological targets

The study of biologically active natural products has resulted in seminal contributions to our understanding of living systems. In the case of electrophilic natural products, the covalent nature of their interaction has largely facilitated the identification of their biological binding partners. In this review, we provide a comprehensive compilation of electrophilic natural products from all major chemical classes together with their biological targets. Covering Michael acceptor systems, ring-strained compounds and other electrophiles, such as esters or carbamates, we highlight representative and instructive examples for over 20 electrophilic moieties. The fruitful cooperation of natural product chemistry, medicinal chemistry and chemical biology has produced a collection of well-studied examples for how electrophilic natural products exert their biological functions that range from antibiotic to antitumor effects. Special emphasis is put on the elucidation of their respective biological targets via activity-based protein profiling, which together with the recent advancements in mass spectrometry has been crucial to the success of the field. The wealth of naturally occurring electrophilic moieties and their chemical complexity enables binding of a large variety of biological targets, such as enzymes of all classes, nonenzymatic proteins, DNA and other cellular compounds. With approximately 30,000 genes in the human genome but only 266 confirmed protein drug targets, the study of biologically active, electrophilic natural products has the potential to provide insights into fundamental biological processes and to greatly aid the discovery of new drug targets.     

Use of quadrupole time of flight mass spectrometry for the characterization of transformation products of the antibiotic sulfamethazine upon photocatalysis with Pd‐doped ceria‐ZnO nanocomposite

The photocatalytic degradation of the antibiotic sulfamethazine under excitation at 365 nm of Pd‐doped ceria‐ZnO nanocomposite, titanium dioxide and iron(III) aqua complex was deeply studied from the analytical point of view. It reveals the formation of nine degradation products that were detected in their protonated forms using LC/electrospray ionization quadrupole time‐of‐flight MS in the positive mode. Their formation involves the hydroxyl radical, and their concentrations increased with irradiation time. Collision‐induced dissociation tandem mass spectrometry associated with the accurate mass measurements was efficiently used for the elucidation of their chemical structures. None of these identified degradation products has been already reported in the literature. Three by‐products result from the hydroxylation at the pyrimidine moiety as well as at the aromatic part, two of them arise from the scission of the pyrimidine group, and finally, three of them come from the scission of the sulfamide bridge. This points the evidence of studying the fate of these degradation products if their toxicity is demonstrated because they are clearly the result of the reaction of hydroxyl radical with the antibiotic sulfamethazine. Copyright © 2015 John Wiley & Sons, Ltd.     

Identification of reactive dyes in spent dyebaths and wastewater by capillary electrophoresis-mass spectrometry

Capillary electrophoresis with diode array detection and mass spectrometry combined with solid-phase extraction were employed for the identification of reactive vinylsulfone and chlorotriazine dyes and their hydrolysis products in spent dyebaths and raw and treated wastewater. Recoveries of dyes from treated wastewater as their tetrabutylammonium ion-pairs using C18 reversed-phase cartridges ranged from 81 to 121%. Detection limits in sewage effluent of the different dyes and hydrolysis products ranged from 23 to 42 microg/l. The method was successfully applied to the detection of the hydrolysis products of five reactive dyes in influents and effluents of a municipal wastewater treatment plant receiving dyehouse effluents.     

LC/MS study of the UV filter hexyl 2‐[4‐(diethylamino)‐2‐hydroxybenzoyl]‐benzoate (DHHB) aquatic chlorination with sodium hypochlorite

The fate of modern personal care products in the environment is becoming a matter of increasing concern because of the growing production and assortment of these compounds. More and more chemicals of this class are treated as emerging contaminants. Transformation of commercially available products in the environment may result in the formation of a wide array of their metabolites. Personal care products in swimming pools and in drinking water reservoirs may undergo oxidation or chlorination. There is much data on the formation of more toxic metabolites from original low toxicity commercial products. Therefore, reliable identification of all possible transformation products and a thorough study of their physicochemical and biological properties are of high priority. The present study deals with the identification of the products of the aquatic chlorination of the hexyl 2‐[4‐(diethylamino)‐2‐hydroxybenzoyl]‐benzoate ultraviolet filter. High‐performance liquid chromatography/mass spectrometry (HPLC/MS) and HPLC/MS/MS with accurate mass measurements were used for this purpose. As a result, three chlorinated transformation products were identified. Copyright © 2013 John Wiley & Sons, Ltd.     

天然产物生物合成:探索大自然合成次生代谢产物的奥秘

天然产物(次生代谢产物)是大自然馈赠给人类的礼物,由于其复杂的骨架结构和良好的药用价值,吸引着化学家们对其进行结构鉴定以及化学合成。尽管人们在天然产物全合成中取得了巨大的成就,但仍然面临着合成路线长、产率低、缺乏选择性等问题。大自然是最伟大的化学家,它利用酶作为催化剂,往往能够高效地合成天然产物。在基因水平上探索大自然合成复杂多样的天然产物的奥秘不仅有助于人们进一步理解和认知有机化学,还为人们开发和利用大自然高效催化化学反应的工具——酶奠定了基础。     

New phomalone derivatives from the endolichenic fungus Cochliobolus kusanoi in Ny‐Alesund Arctic

Natural products from endolichenic fungi, isolated from different lichen species, have been attracting much attention because of their potential to produce metabolites with activities and/or new structures. The filamentous fungus M227‐2 isolated from lichen in Ny‐Alesund Arctic showed significant anti‐microbial activity and was identified as Cochliobolus kusanoi based on 18S rDNA. Secondary metabolites of M227‐2 were investigated in order to exploit them as lead compounds for new antibiotics. Chemical investigation on M227‐2 led to the isolation of three phomalone derivatives (products 1 – 3) . Their structures were elucidated on the basis of their NMR and MS spectral data. Product 2 was new, whereas products 1 and 3 were isolated for the first time from the species. The biosynthetic pathway is also proposed.     

Simultaneous analysis of current‐use pesticides and their transformation products in water using mixture‐sorbent solid phase extraction and high‐performance liquid chromatography–tandem mass spectrometry

Pesticides have posed significant threats to aquatic ecosystems, yet little is known about their transformation products. The challenge is to simultaneously analyze various pesticides and transformation products in water as they have distinct physicochemical properties. A mix‐mode solid phase extraction method was established to simultaneously analyze current‐use pesticides and their transformation products using a mixture of hydrophile–lipophile balance, weak anion, and cation exchange resins (2:1:1, w/w/w) in combination with high‐performance liquid chromatography and tandem mass spectrometry for chemical quantification. Neutral, acidic, and alkaline methanol were used as the elution solvent. Box‐Behnken design was applied to optimize extraction conditions. Optimal conditions were as follows: sorbent mass, 200 mg; volume of elution solvent, 5 mL × 3; pH 4. The method was validated for compounds at concentrations from 20 to 1000 ng/L in different types of water samples, with recovery being from 43.5 ± 3.1 to 141 ± 35%. Low method detection limits (0.02?5.6 ng/L) implied that the developed method was sensitive. Finally, the method was applied to monitor current‐use pesticides and their transformation products in natural waters. Frequent detection of transformation products of pesticides indicated that their contribution to aquatic risk should not be ignored.     

The S2 emission characteristics of several organic sulfur compounds obtained by molecular emission cavity analysis and pyrolysis

Emission profiles of several organic sulfur compounds are investigated by modified molecular emission cavity analysis (MECA). Thiourea, 1,3-diethylthiourea, S-methyl- cysteine and taurine are pyrolyzed in a hydrogen stream and the pyrolytic products are determined by gas chromatography. The S₂ emission mechanism is discussed on the basis of emission profiles and the composition of the pyrolytic products. Although some compounds give multipeaked responses, the splitting disappears when a worn surface cavity is used or oxalic acid is added to the sulfur compound in the cavity. When the emission profile from thiourea is compared with that from 1,3-diethylthiourea, it is clear that the multipeaked response is due to quenching by degradation products of the latter compound. The main product of pyrolysis is hydrogen sulfide. The emission intensity is related to the yield of hydrogen sulfide in pyrolysis. As methylmercaptan was not detected in the pyrolysis products, it is suggested that the quenching by the organic fragments results from their hydrogen consumption rather than their reaction with sulfur species. The S₂ emission from sulfur-containing compounds is rapidly complete in the presence of oxalic acid, and it is suggested that such compounds are subject to reductive breakdown in the cavity.     

Characterisation of the oxidation products of pyrite by Thermogravimetric and Evolved Gas analysis

Museum specimens of pyrite are known to undergo oxidation even during storage. Characterisation of the oxidation products is however not always simple due to amorphous character and varying degrees of hydration of the oxidation products. This paper presents an alternative approach to the characterisation of oxidation products by identifying their presence from their characteristic thermal decomposition processes using thermogravimetric and evolved gas analysis. Four pyrite specimens were characterised with varying degrees of oxidation. Iron(II) and iron(III) sulphates were also characterised for comparative purposes. The degradation products were observed to correlate well with the presence of iron(II) sulphate even though there was found to be some discrepancy in the higher temperature decomposition reactions. This revised version was published online in July 2006 with corrections to the Cover Date.     

Synthesis of 3-benzoyl-4-benzylfurans structural related to furolignans

Abstract

Furolignan-type natural products, possessing important biological properties, have been synthesized from a commercially available furan. The elaborated synthetic strategy is based on an innovative Friedel-Crafts reaction starting from an alcohol or a carboxylic acid and triflic anhydride as promoter. Through this synthetic strategy, furolignans having two different aryl groups have been obtained. The products have been evaluated for their antimicrobial properties on Gram positive and Gram negative bacteria, in order to compare their biological activities with those of natural analogues.     

Beseitigung des Matrixeffekts bei der Analyse von Edelmetallspuren mit induktiv gekoppeltem Plasma

Summary Spectral interferences associated with the determination of trace contents of Au, Ag, Pt and Pd in samples with complex matrices (hydrometallurgical solutions, metallurgical products and ore processing products) were investigated. It was found that it is necessary to separate Au, Pt and Pd from the matrix elements. The results obtained with various methods for separation and pre-concentration of these elements showed that in the case of hydrometallurgical solutions adsorption on activated carbon satisfies the requirements of analytical control. For the determination of these elements in ore processing products it is necessary to use additional extraction for their preconcentration. The most suitable organic solution found for the extraction of Au, Pt and Pd and their determination with ICP is isoamyl alcohol.     

Evaluation of thin-layer chromatography methods for quality control of commercial products containing Aesculus hippocastanum, Turnera diffusa, Matricaria recutita, Passiflora incarnata, and Tilia occidentalis

In Mexico, plant-derived products with health claims are sold as herbal dietary supplements, and there are no rules for their legal quality control. Aesculus hippocastanum, Turnera diffusa, Matricaria recutita, Passiflora incarnata, and Tilia occidentalis are some of the major commercial products obtained from plants used in this region. In this paper, we describe the effectiveness of thin-layer chromatography methods to provide for the quality control of several commercial products containing these plants. Standardized extracts were used. Of the 49 commercial products analyzed, only 32.65% matched the chromatographic characteristic of standardized extracts. A significant number of commercial products did not match their label, indicating a problem resulting from the lack of regulation for these products. The proposed methods are simple, sensitive, and specific and can be used for routine quality control of raw herbals and formulations of the tested plants. The results obtained show the need to develop simple and reliable analytical methods that can be performed in any laboratory for the purpose of quality control of dietary supplements or commercial herbal products sold in Mexico.     

Elongation of β-hydroxyenones by cross-metathesis

Enantioenriched aldol products derived from enones are notoriously difficult to prepare due to their sensitivity to retro-aldolisation, elimination and the requirement of a large excess of the enone donor for their preparation. However, some success has been obtained for the preparation of aldol products derived from methylvinylketone and pentenone using zinc-dinuclear catalysts or catalytic antibodies. Herein, we describe how simple first-generation hydroxyenones can be easily elongated by alkene exchange with structurally diverse olefinic partners in the presence of Ru-based metathesis catalysts allowing for the preparation of aldol products difficult to access by direct aldolisation. The data suggest that even though unprotected aldols are suitable for these cross-metathesis reactions, silyl-protected β-hydroxyenones generally afforded the desired elongated products in much higher chemical yields.     

Mechanism of antioxidant action. Transformation involved in the antioxidant function of nickel dithiolates—2

The initial transformation products from nickel dialkyl dithiophosphates and nickel alkyl xanthates have been identified by spectrophotometric and kinetic methods. A common mechanism of action is involved for both nickel complexes and the distribution of products from complexes during their reaction with hydroperoxides suggests a greater contribution from an ionic mechanism in the case of dithiophosphate. Nickel dialkyl dithiophosphate is more stable to u.v. light than nickel alkyl xanthate and its reaction with tert. butyl hydroperoxide in the presence and absence of light is 7–8 times faster than that of the xanthate.