Ethyl lactate and its aqueous solutions as sustainable media for organic synthesis

Ethyl lactate is an amphiphilic bio-based solvent with beneficial safety characteristics and ecotoxicity profile. The miscibility of ethyl lactate with water allows adjustments of the medium properties using aqueous solutions of various concentrations to achieve the desired reaction outcome. This review discuses current applications of ethyl lactate and its aqueous solutions as media for organic synthesis. The effectiveness of these media has been demonstrated in several coupling reactions, olefin metathesis, carbonyl group reactions, heterocyclizations, various multicomponent reactions and other chemical transformations. These reactions often benefit from the application of non-conventional energy sources (microwave, ultrasound, and visible light irradiation). The reaction yields are typically comparable or higher than that obtained in conventional solvents.     

Surface and emulsifying properties of raw ethanolic extracts from legumes containing soyasaponins and proteins

The development of new amphiphilic compounds of natural origin is a challenging field of research in surfactant science. In this scenario, surfactants obtained from renewable organic sources is a valuable option to be exploited. The present work proposes raw ethanolic extracts containing soyasaponins, proteins and polysaccharides from legumes as surface active mixtures and stabilizers for emulsified systems. These extracts are produced by a green extraction process using an hydroalcoholic mixture (70:30 w/w) as solvent and six different legumes soybean, lentils, peas, beans, chickpeas, wild peas as starting materials. After freeze-drying, extracts were characterized in terms of total soyasoponin (from 1377 to 7354 mg/100 g), soyasaponin I (from 15 to 1459 mg/kg), soyasaponin VI (from 13 to 1076 mg/kg) and protein (16–28 g/100 g) contents. All extracts aqueous solutions show good surface active properties, being able to reduce the air-water surface tension to values comparable to those of the commonly employed surfactants (28–33 mN/m). Differences are observed in terms of emulsifying ability, since only lentils and soybeans extracts, thanks to their high soyasaponins and protein content, can act as stabilizers for emulsions containing up to 10% w/w of ethyl oleate (as oil phase) over six months of storage at 4 °C. These extracts are promising amphiphilic natural mixtures, potentially employable for food or pharmaceutical applications. Their relevance is also related to the possibility of using legumes derived from industrial wastes of food manufacturing, thereby giving valorization of by-products and residues in the context of a “circular economy” model.     

Comparative hemolytic activity of undiluted organic water-miscible solvents for intravenous and intra-arterial injection

In humans, nonaqueous solvents are administered intravascularly in two kinds of situations. They have been used in subcutaneous or intramuscular pharmaceutical formulations to dissolve water-insoluble drugs. The need for these vehicles had increased in recent years, since the drug development process has yielded many poorly water-soluble drugs. The use of water-miscible nonaqueous solvents in therefore one of the approaches for administering these products as reference solutions useful in formulation bioequivalence studies. The intravascular use of organic solvents has also gained importance owing to a new approach for the treatment of cerebral malformations using precipitating polymers dissolved in water-miscible organic solvents. At present, the solvent most commonly used for the liquid embolics to solubilize the polymers is dimethyl sulfoxide, which exhibits some local and hemodynamic toxicities. In order to find new, less toxic vehicles for pharmaceutical formulations for the intravenous and intra-arterial routes and for embolic materials, 13 water-miscible organic solvents currently used (diluted with water) for pharmaceutical applications, were evaluated in this study. Their hemolytic activity and the morphological changes induced when mixed with blood (1:99, 5:95, 10:90 solvent:blood) were estimated in vitro. From these data, the selected organic solvents could be subdivided into four groups depending on their hemolytic activity: very highly hemolytic solvents (ethyl lactate, dimethyl sulfoxide), highly hemolytic solvents (polyethylene glycol 200, acetone), moderately hemolytic solvents (tetrahydrofurfuryl alcohol, N-methyl-2-pyrrolidone, glycerol formal, ethanol, Solketal, glycofurol) and solvents with low hemolytic activity (propylene glycol, dimethyl isosorbide, diglyme).     

Antioxidant,anti-microbial and antimutagenicity activities of pistachio (Pistachia vera) green hull extract

Antioxidant, anti-microbial and antimutagenicity activities of pistachio (Ahmadaghaei variety) green hull extracts (crude and purified extracts) were studied. At first, different solvents were compared for determining of the best solvent for extraction of phenolic compounds from pistachio green hull. Water and acetonitrile with 49.32 and 6.22 (mg of gallic acid equivalents/g sample) were the best and the worst solvent in the extraction of phenolic compounds, respectively. The antioxidant capacity of crude and purified extracts were assessed through ABTS assay, DPPH assay and β-carotene bleaching (BCB) method. A concentration-dependent antioxidative capacity was verified in ABTS, DPPH assays and BCB method. The anti-microbial capacity was screened against Gram positive and Gram negative bacteria, and fungi. Aqueous and purified extracts inhibited the growth of Gram positive bacteria; Bacillus cereus was the most susceptible one with MIC of 1 mg/mL and 0.5 mg/mL for the crude and purified extracts, respectively. The results of antimutagenicity test showed that phenolic compounds of pistachio green hull have antimutagenicity activity against direct mutagen of 2-nitrofluorene. The results obtained indicate that pistachio green hull may become important as a cheap and noticeable source of compounds with health protective potential and anti-microbial activity.     

Pharmaceutical applications of supercritical carbon dioxide.

The appearance of a supercritical state was already observed at the beginning of the 19th century. Nevertheless, the industrial extraction of plant and other natural materials started about twenty years ago with the decaffeination of coffee. Today carbon dioxide is the most common gas for supercritical fluid extraction in food and pharmaceutical industry. Since pure supercritical carbon dioxide is a lipophilic solvent, mixtures with organic solvents, especially alcohols, are used to increase the polarity of the extraction fluid; more polar compounds can be extracted in this way. The main fields of interest are the extraction of vegetable oils from plant material in analytical and preparative scale, the preparation of essential oils for food and cosmetic industry and the isolation of substances of pharmaceutical relevance. Progress in research was made by the precise measurement of phase equilibria data by means of different methods. Apart from extraction, supercritical fluid chromatography was introduced in the field of analytics, as well as micro- and nanoparticle formation using supercritical fluids as solvent or antisolvent. This review presents pharmaceutical relevant literature of the last twenty years with special emphasis on extraction of natural materials.     

Deep eutectic solvents as sustainable extraction media for plants and food samples: A review

With the introduction of the concept of green chemistry, eco-friendly extraction processes are moving from an option to a must. Therefore, the discovery and development of new solvents with less hazardous ecotoxicological profiles are required urgently to replace, reduce, or even eliminate petroleum ones. Recently, making up a novel class of solvents as an alternative to ionic liquids (ILs), natural deep eutectic solvents, NADES might be considered as one of the most promising discoveries in the field of green chemistry. Investigated as potential green tools and especially in the field of extraction of valuable compounds from medicinal plants and food. In this article, we attempt to provide an overview of knowledge regarding natural DESs as novel solvents technology. Their formation, structure, some physicochemical properties, and especially, with emphasis on their beneficial applications in the extraction and separation process of valuable compounds from different plants families and food samples. Biological activities and industrial application of eutectic bio extracts are summarized, and further perspectives are discussed.     

CuBr2/O2促进N-芳基-β-烯胺酯分子内氧化环合反应构建2,3-二取代吲哚

吲哚类化合物作为一类具有广泛生物和药理活性的有机分子,其合成研究具有重要的价值。而通过N-芳基烯胺的分子内氧化偶联反应构建吲哚类化合物成为合成吲哚类化合物最直接、高效的方法之一,得到合成化学家的广泛关注。基于此,本文发展以便宜的二价铜盐(CuBr2)、绿色氧化剂(O2)和吡啶作为配体共同促进的N-芳基-β-烯胺酯的分子内氧化环合反应,以58%~94%的收率成功地合成一系列2,3-二取代的吲哚类化合物,并对其进行核磁共振氢谱和碳谱表征。该合成策略为吲哚类化合物的合成提供了新的方法。     

Role of micellar nanoreactors in organic chemistry: Green and synthetic surfactant review

Over the last few decades surface active compounds in aqueous media have proven to be the most benign alternative for overcoming the difficulty of insolubility and hydrolytic breakdown of numerous non-polar compounds in aqueous medium. Surfactants have the unique ability to from micelles when they reach the critical micelle concentration, form emulsion and also help in solubilizing immiscible organic reagents in organic reactions and hence are a valuable asset in organic chemistry. Biosurfactants or green surfactants are amphiphilic compounds, often extracellularly secreted by variety of plants, animals and microorganisms as a means of secondary metabolites by utilizing varieties of waste raw materials and are a promising candidate to replace harmful organic solvents as well as synthetically designed surfactants owing of their remarkable traits like low toxicity, functionality under adverse conditions, based on renewable ingredients, and biodegradable nature, there is growing interest in this issue. Numerous organic reactions in water are now possible without the use of rather toxic and non-biodegradable organic solvents, thanks to the advent of new and greener biosurfactants into the field of organic chemistry.     

Food and Drug Administration proposed testing guidelines for reproduction studies. Revision Committee. FDA Guidelines for Developmental Toxicity and Reproduction, Food and Drug Administration.

In the United States, the Food and Drug Administration (FDA) is the agency responsible for ensuring that the direct food additives and color additives used in food are safe for all consumers. In order to determine the safety of these additives for consumption, appropriate information and results from a series of tests must be made available to the agency. In 1982, in an effort to provide guidance to the food industry concerning the appropriate tests for the determination of safety, the FDA issued the Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Foods, commonly referred to as the Redbook. In 1993, based on the expansion of technology and the use of food additives, as well as the refinement of the scientific criteria for establishing safety, the FDA updated its guidelines and issued the draft Redbook II. Since Redbook II was issued, additional refinements have been made in the procedures for the multigeneration reproduction study and for the assessment of effects on male reproduction. The latest proposed guidelines for multigeneration studies are provided here.     

Unified Physicochemical Property Estimation Relationships (UPPER)

The knowledge of physicochemical properties of organic compounds becomes increasingly important in pharmaceutical sciences, chemical engineering, and other fields. In this study, we developed UPPER (Unified Physicochemical Property Estimation Relationships), a comprehensive model for the estimation of 20 physicochemical properties of organic compounds. UPPER is a system of thermodynamically sound relationships that relate the various phase-transition properties to one another, which includes transition heats, transition entropies, transition temperatures, molar volume, vapor pressure, solubilities and partition coefficients in different solvents, and so on. UPPER integrates group contributions with the molecular geometric factors that affect transition entropies. All of the predictions are directly based on molecular structure. As a result, the proposed model provides a simple and accurate prediction of the properties studied. UPPER is designed to predict industrially, pharmaceutically, and environmentally relevant physicochemical properties. It can be an aid for the efficient design and synthesis of compounds with optimal physicochemical properties.     

保健品固体制剂中10种残留溶剂GC分析及GC-MS确证

目的 建立可同时定性定量检测保健食品固体制剂中甲醇、乙醇、丙酮、异丙醇、正己烷、乙酸乙酯、苯、1,2-二氯乙烷、正丁醇、二乙烯苯10种残留溶剂的方法。方法 气相色谱-FID检测器,色谱柱为DB-624毛细管色谱柱;GC-MS-EI离子源,色谱柱为DB-624MS毛细管色谱柱。结果 各有机溶剂线性关系良好（r〉0.99）,平均回收率为85.2%~108.6%,RSD为1.0%~3.1%。结论 本方法简便准确、灵敏度高,检出限都低于中国药典2010年版二部附录ⅧP中有机溶剂允许残留量的要求,适用于保健食品固体制剂中有机溶剂残留量的同时测定。     

顶空气相色谱法测定比阿培南的有机溶剂残留量

目的测定比阿培南中有机溶剂残留量。方法采用顶空进样法测定,检测器为FID,色谱柱为SE-54毛细管柱,溶剂为5%二甲基亚砜水溶液。结果甲醇、乙醇、乙腈、二氯甲烷、乙酸乙酯、甲酸乙酯、异丙醚、四氢呋喃、正丙醇线性关系r在0.9938～0.9994范围内;平均回收率在94.87%～105.66%范围内,RSD在2.11%～6.94%范围内(n=5)。结论该方法简单、准确、快捷,适用于测定比阿培南中有机溶剂残留量。     

Development of natural pigments from Tectona grandis (teak) leaves: Agricultural waste material from teak plantations

The purpose of the research was to develop a new pigment from teak leaves, an agricultural waste material from the teak industry. Teak leaves were extracted by various polarity solvents to provide a variety of color extracts. The ethyl acetate extract gave reddish-brown with the highest intensity. The ethyl acetate extract was selected to develop the pigment by adsorption method. It was found that the type of substrate affects the color and the intensity of the obtained pigments. Using aluminium hydroxide Al(OH)₃ as a substrate provided the purple pigment with the highest color intensity because Al(OH)₃ could adsorb both flavonoids and anthraquinones contained in the extract. The other substrates showed a lighter color because they could adsorb only flavonoids. Increasing the mass ratio between Al(OH)₃ and the extract, when preparing the pigment, increased the color intensity of the pigment, with a mass ratio of 10:5, resulting in the color compounds in the pigment being in the range of 12–20%, which meets commercial requirements. The pigments also exhibited higher thermal and light stability than the extract. These results demonstrate the possibility of teak leaves being used as a new source for the development of natural pigments in cosmetic products.     

Fluorescent labeling of drugs and simple organic compounds containing amine functional groups, utilizing dansyl chloride in Na(2)CO(3) buffer.

Fluorescent labeling of amine functional groups using dansyl chloride (DNS-Cl), and in sodium carbonate buffer, allowed the detection of 1 microg amounts of analytes. The methodology presented allows dansylation of primary, secondary, and tertiary amine groups at a temperature of 25 degrees C. The dansylation of tertiary amines involves a chemical reaction which removes one substituent (or branch) of the amine group. A one molar working concentration of Na(2)CO(3) is used, and is at pH 11.0. Compounds such as isopropylamine, dipropylamine, diethylamine, triethylamine, triisooctylamine, and N,N-dimethylaniline were labeled by use of DNS-Cl from samples obtained from a complex mixture of alkanes. The compound p-chloroaniline contains a primary amine group and is a solid at 25 degrees, quickly dissolves in the one molar sodium carbonate buffer and is dansylated in 15 min. Heroin, which contains a tertiary amine group, was extracted into ethyl acetate from an aqueous solution, then reacted with DNS-Cl. Benzocaine, a local anesthetic, was dansylated in 15 min. Tertiary amine groups incorporated in a rigid ring system, such as for caffeine, strychnine, and the ionic salt form of cocaine hydrochloride did not react with DNS-Cl under these conditions. The reaction time for tertiary amines was 2 h or less, and 15 min for compounds having primary and secondary amine groups. Separation of the dansylated compounds from unreacted DNS-Cl was accomplished by diethyl ether extraction of the aqueous reaction solution, followed by thin layer chromatography using various organic solvents such as acetone and methylene chloride.     

Valorisation of waste chicken feathers: Optimisation of decontamination and pre-treatment with bleaching agents using response surface methodology

Environmental concerns, rapid oil consumption, the high price of oil, and limited oil reserves are driving research into cheap, biodegradable, sustainable, renewable, and abundantly available green materials. Waste chicken feathers are abundant and cheap by-products from poultry processing plants and their beneficiation offers possible solutions to these issues. Raw chicken feathers are wastes that are mixed with offal fat, debris, blood, preen oil and other wastes from the poultry process. Consequently, feathers are hazardous wastes that are contaminated with bacteria, which makes them odoriferous and unfit for valorisation as is. These contaminants must be removed before possible valorisation otherwise the feathers will not fit for purpose. The effects of oxidative (hydrogen peroxide and sodium hypochlorite) and reductive (Sodium dithionite) compounds as decontamination agents were studied on chicken feathers to assess their decontamination and pre-treatment efficiency and their effects on physicochemical and mechanical properties of the feathers. Statistically designed experiments were used to optimise the decontamination process using response surface methodology with a Box-Behnken experimental design. Regression equations were obtained to analyse microbial count and the optimum process parameters were identified. Under optimised conditions, the treated chicken feathers were characterised and their properties compared with those of unwashed chicken feathers. From the results, it was deduced that the inorganic bleaching treatments were effective removing the microbial impurities from the feathers and their use resulted in enhanced physicochemical properties of the chicken feathers. The untreated chicken feathers had the highest microbial counts (1.48E+ 07 ± 6.72E05 Cfu/g) whereas decontaminated samples showed a reduction in thousand-fold. The impurity removal after washing was about 8–18%.     

Cyrene: A bio-based sustainable solvent for organic synthesis

Cyrene (dihydrolevoglucosenone) is a green dipolar aprotic solvent prepared by pyrolysis of cellulose-containing biomass. Cyrene possesses a beneficial occupational health and safety profile combined with good biodegradability without NO_x or SO_x production. Since 2014, when Cyrene was for the first time introduced as a green solvent, it has attracted much attention in different fields. In this review, we discuss organic reactions, for which Cyrene was employed to play the role of medium. Significant progress was achieved in the replacement of conventional aprotic solvents by Cyrene as a safe and sustainable alternative. Cyrene demonstrated to be an effective medium for diverse chemical transformations, from carbon-carbon coupling reactions to bio-catalyzed processes and polymerization. The applications of Cyrene as a co-solvent (e.g. in form of aqueous solutions) for organic synthesis are also discussed.     

Activity of compounds from Chinese herbal medicine Rhodiola kirilowii (Regel) Maxim against HCV NS3 serine protease

Treatment of the chronic hepatitis C virus (HCV) infection is an unmet medical need, and the HCV NS3 serine protease (NS3-SP) has been used as an attractive target of antiviral screening against HCV. To find naturally chemical entities as lead compounds from which novel anti-HCV agents could be developed, bioassay-guided fractionation and isolation were performed on a crude ethanol extract from rhizomes of the Chinese medicinal herb Rhodiola kirilowii (Regel) Maxim using column chromatography (CC) techniques and in vitro inhibitory activity against HCV NS3-SP. The partition of the extract between water and different organic solvents led to the isolation and identification of 12 compounds in the ethyl acetate part which proved to be the most active. These compounds were tested for in vitro activity against HCV NS3-SP, among which four (-)-Epicatechin derivatives: 3,3'-Digalloylproprodelphinidin B2 (Rhodisin, 1); 3,3'-Digalloylprocyanidin B2 (2); (-)-Epigallocatechin-3-O-gallate (EGCG, 3); and (-)-Epicatechin-3-O-gallate (4, ECG) represented the most potent ones with IC(50) of 0.77, 0.91, 8.51, and 18.55 microM, respectively. Salidroside, the commonly known compounds, together with the other compounds showed no activity up to 100.0 microM. Methylation and acylation of the hydroxyl groups of 1-4 caused a decrease of activity. Cell viability and secreted alkaline phosphatase (SEAP) activity assays with 1-4 revealed little if any toxicity. These nonpeptide inhibitors of HCV NS3-SP might serve as potential candidate anti-HCV agents.     

The evaluation of five bioactive compounds content and in vitro antioxidant of Caryophylli Flos extracts obtained by natural deep eutectic solvents

In this study, a simple, green and efficient method based on ultrasound-assisted NADESs was used to extract ellagic acid, isoquercitrin, myricetin, luteolin and eugenol from Caryophylli Flos. Nine different NADESs were synthesized and screened, and 1,3-butanediol-levulinic acid (molar ratio 1: 3) was selected as the topgallant solvent for maximizing target compounds extraction yields. Single factor experiments combined with response surface methodology and genetic algorithm were applied for efficient optimization of the main variables in the extraction procedure. The optimum experimental conditions were as follows: water content in NADES 29%, liquid-solid ratio 21 mL/g and extraction time 30 min. After the optimization of several main variables, an extract obtained showed higher extraction yields and DPPH and ABTS radical scavenging rate than conventional organic solvents extracts which were used for comparison. Consequently, this study provides a suitable strategy for efficiently extracting bioactive compounds from Caryophylli Flos, and NADESs can be employed as green extraction media for obtaining other natural products.     

Evaluation of potential neurotoxic effects of occupational exposure to (L)-lactates

Organo psycho syndrome (OPS) or chronic toxic encephalopathy (CTE) is a neurotoxic condition reported following long-term exposure to paints containing organic solvent and to other solvents. Lactate esters are finding wider use as solvents. Lactate esters have been well studied in standard toxicity tests, but specific neurotoxicity studies have not been conducted. No clinical signs of chronic neurotoxicity have been observed in standard toxicity tests. Lactate esters are rapidly hydrolyzed in the body to lactic acid and the corresponding alcohol. Alcohols have been reported to have acute neurotoxic effects, usually following high levels of ingestion. The literature on alcohols was reviewed to establish the no-observed-adverse-effect level (NOAEL) for acute neurotoxicity and to look for any evidence of chronic neurotoxicity from the alcohols produced by hydrolysis of the lactate esters. The NOAELs were compared with the potential amounts of alcohol produced by hydrolysis of different lactate esters at 200 mg//m(3) (the NOAEL for most of the lactate esters). In all cases neither acute nor chronic neurotoxicity would be expected based on the amounts of alcohol produced by hydrolysis of the lactate esters at their NOAELs. L-Lactic acid is a normal metabolite in the body and is not considered neurotoxic. Based on this information there is no evidence to suggest that L-lactate esters can cause any chronic neurotoxicity, OPS, or CTE.