Showing papers by "Christian V. Stevens published in 2016"
TL;DR: This review covers some of the latest and most relevant developments in the field of continuous flow chemistry with the focus on hazardous reactions.
Abstract: Over the last two decades, flow technologies have become increasingly popular in the field of organic chemistry, offering solutions for engineering and/or chemical problems. Flow reactors enhance the mass and heat transfer, resulting in rapid reaction mixing, and enable a precise control over the reaction parameters, increasing the overall process selectivity, efficiency and safety. These features allow chemists to tackle unexploited challenges in their work, with the ultimate objective making chemistry more accessible for laboratory and industrial applications, avoiding the need to store and handle toxic, reactive and explosive reagents. This review covers some of the latest and most relevant developments in the field of continuous flow chemistry with the focus on hazardous reactions.
490 citations
TL;DR: This review summarizes recent literature on the synthesis and pharmaceutical properties of pyrrolopyrimidines and contains a description of common retro-synthetic strategies, with particular attention for newly reported synthetic entries to the scaffold.
Abstract: This review summarizes recent literature (2000–2015) on the synthesis and pharmaceutical properties of pyrrolopyrimidines. These modified pyrimidine bases, fused to a pyrrole ring, and their corresponding nucleosides display a broad applicability in medicinal chemistry. This overview is divided into three main sections, according to the respective isomers: pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, and pyrrolo[3,4-d]pyrimidines. Each section contains a description of common retro-synthetic strategies, with particular attention for newly reported synthetic entries to the scaffold. Next, the synthetic strategies and the ways in which the scaffolds can be further modified are exemplified according to the biological properties of the obtained products.
124 citations
TL;DR: This work uses pH-resolved in situ small angle X-ray scattering (SAXS) under synchrotron radiation to characterize the pH-dependent mechanism of evolution from micelles to the more complex aggregates at acidic pH.
Abstract: A set of four structurally related glycolipids are described: two of them have one glucose unit connected to either stearic or oleic acid, and two other ones have a diglucose headgroup (sophorose) similarly connected to either stearic or oleic acid. The self-assembly properties of these compounds, poorly known, are important to know due to their use in various fields of application from cleaning to cosmetics to medical. At basic pH, they all form mainly small micellar aggregates. At acidic pH, the oleic and stearic derivatives of the monoglucose form, respectively, vesicles and bilayer, while the same derivatives of the sophorose headgroup form micelles and twisted ribbons. We use pH-resolved in situ small angle X-ray scattering (SAXS) under synchrotron radiation to characterize the pH-dependent mechanism of evolution from micelles to the more complex aggregates at acidic pH. By pointing out the importance of the COO–/COOH ratio, the melting temperature, Tm, of the lipid moieties, hydration of the glycosi...
74 citations
TL;DR: It is demonstrated that the aqueous self-assembly at room temperature of a family of β-d-glucose microbial glycolipids bearing a saturated and monounsaturated C18 fatty acid chain cannot be explained on the simple basis of the well-known packing parameter, and it is shown that this behavior can be explaining on the different bilayer membrane elasticity as a function of temperature.
Abstract: Microbial glycolipids are a class of well-known compounds, but their self-assembly behavior is still not well understood. While the free carboxylic acid end group makes some of them interesting stimuli-responsive compounds, the sugar hydrophilic group and the nature of the fatty acid chain make the understanding of their self-assembly behavior in water not easy and highly unpredictable. Using cryo-transmission electron microscopy (cryo-TEM) and both pH-dependent in situ and ex situ small angle X-ray scattering (SAXS), we demonstrate that the aqueous self-assembly at room temperature (RT) of a family of β-d-glucose microbial glycolipids bearing a saturated and monounsaturated C18 fatty acid chain cannot be explained on the simple basis of the well-known packing parameter. Using the “pH-jump” process, we find that the molecules bearing a monosaturated fatty acid forms vesicles below pH 6.2, as expected, but the derivative with a saturated fatty acid forms infinite bilayer sheets below pH 7.8, instead of ves...
64 citations
TL;DR: The significance of renewable resources within the chemical industry is constantly increasing as mentioned in this paper and they serve as alternatives for fossil resources whose supply is limited and who have a major impact on the environment.
42 citations
TL;DR: The influence of fruit origin on the vegetable oil composition was shown to be very important, particularly in terms of the phospholipids, sterols, and tocols composition.
Abstract: Coriander vegetable oil was extracted from fruits of French origin in a 23% yield. The oil was of good quality, with a low amount of free fatty acids (1.8%) and a concurrently high amount of triacylglycerols (98%). It is a rich source of petroselinic acid (C18:1n-12), an important renewable building block, making up 73% of all fatty acids, with also significant amounts of linoleic acid (14%), oleic acid (6%), and palmitic acid (3%). The oil was characterized by a high unsaponifiable fraction, comprising a substantial amount of phytosterols (6.70 g/kg). The main sterol markers were β-sitosterol (35% of total sterols), stigmasterol (24%), and Δ7-stigmastenol (18%). Squalene was detected at an amount of 0.2 g/kg. A considerable amount of tocols were identified (500 mg/kg) and consisted mainly of tocotrienols, with γ-tocotrienol as the major compound. The phospholipid content was low at 0.3%, of which the main phospholipid classes were phosphatidic acid (33%), phosphatidylcholine (25%), phosphatidylinositol (17%), and phosphatidylethanolamine (17%). About 50% of all phospholipids were non-hydratable. The β-carotene content was low at 10 mg/kg, while a significant amount of chlorophyll was detected at about 11 mg/kg. An iron content of 1.4 mg/kg was determined through element analysis of the vegetable oil. The influence of fruit origin on the vegetable oil composition was shown to be very important, particularly in terms of the phospholipids, sterols, and tocols composition.
42 citations
TL;DR: Both petroselinic acid based sophorolipids displayed a much lower CMC value than their oleic acid based counterparts, although their minimal surface tension was the same.
Abstract: Petroselinic acid, a positional isomer of oleic acid, was isolated from the vegetable oil of Coriandrum sativum fruits. This uncommon fatty acid was subsequently used as substrate for sophorolipid fermentation with a Starmerella bombicola lactone esterase overexpression (oe sble) strain. A petroselinic acid based diacetylated sophorolipid lactone was obtained in high purity without incorporation of de novo synthesized fatty acids such as oleic acid. A total production of 40 g/L was obtained. The petroselinic acid based sophorolipid lactone was subsequently hydrolyzed towards the petroselinic acid based sophorolipid acid. For both compounds, their critical micelle concentration (CMC) and corresponding surface tension were compared to their oleic acid based counterparts. Both petroselinic acid based sophorolipids displayed a much lower CMC value than their oleic acid based counterparts, although their minimal surface tension was the same. Besides, the sophorolipid fermentation product was chemically modified towards a novel C12 sophorolipid aldehyde. This derivative constitutes an interesting building block for further modification towards new-to-nature sophorolipids with high potential for self-assembly applications.
40 citations
TL;DR: Extraction and esterification can be tailored using mixed-anion ionic liquids; this is demonstrated herein using a common trihexyl(tetradecyl)phosphonium cation and a mixed chloride and bis(trifluoromethylsulfonyl)imide anion ions.
Abstract: Ionic liquids can both act as a solvent and mediate esterification to valorize low-titer volatile fatty acids and generate organic solvents from renewable carbon sources including biowaste and CO2. In this study, four phosphonium ionic liquids were tested for single-stage extraction of acetic acid from a dilute stream and esterification to ethyl acetate with added ethanol and heat. The esterification proceeded with a maximum conversion of 85.9±1.3 % after 30 min at 75 °C at a 1:1 stoichiometric ratio of reactants. Extraction and esterification can be tailored using mixed-anion ionic liquids; this is demonstrated herein using a common trihexyl(tetradecyl)phosphonium cation and a mixed chloride and bis(trifluoromethylsulfonyl)imide anion ionic liquid. As a further proof-of-concept, ethyl acetate was generated from an ionic liquid-driven esterification of an acetic acid extractant generated using CO2 as the only carbon source by microbial electrosynthesis.
31 citations
TL;DR: Carbonate microparticles containing a sufficient amount of Mg induced GG hydrogel formation, resulting in injectable, cytocompatible hydrogal-microparticle composites, which can be improved by incorporation of an inorganic phase in particle form, thus maintaining hydrogels injectability.
Abstract: The suitability of hydrogel biomaterials for bone regeneration can be improved by incorporation of an inorganic phase in particle form, thus maintaining hydrogel injectability. In this study, carbonate microparticles containing different amounts of calcium (Ca) and magnesium (Mg) were added to solutions of the anionic polysaccharide gellan gum (GG) to crosslink GG by release of Ca2+ and Mg2+ from microparticles and thereby induce formation of hydrogel-microparticle composites. It was hypothesized that increasing Mg content of microparticles would promote GG hydrogel formation. The effect of Mg incorporation on cytocompatibility and cell growth was also studied. Microparticles were formed by mixing Ca2+ and Mg2+ and [Formula: see text] ions in varying concentrations. Microparticles were characterized physiochemically and subsequently mixed with GG solution to form hydrogel-microparticle composites. The elemental Ca:Mg ratio in the mineral formed was similar to the Ca:Mg ratio of the ions added. In the absence of Mg, vaterite was formed. At low Mg content, magnesian calcite was formed. Increasing the Mg content further caused formation of amorphous mineral. Microparticles of vaterite and magnesium calcite did not induce GG hydrogel formation, but addition of Mg-richer amorphous microparticles induced gelation within 20 min. Microparticles were dispersed homogeneously in hydrogels. MG-63 osteoblast-like cells were cultured in eluate from hydrogel-microparticle composites and on the composites themselves. All composites were cytocompatible. Cell growth was highest on composites containing particles with an equimolar Ca:Mg ratio. In summary, carbonate microparticles containing a sufficient amount of Mg induced GG hydrogel formation, resulting in injectable, cytocompatible hydrogel-microparticle composites.
29 citations
Journal Article•
TL;DR: Hydrogels of Gellan Gum, a biocompatible polysaccharide, were mineralized biomimetically with CaCO 3 using a double enzymatic approach to promote proliferation and spreading of osteoblast-like cells.
20 citations
TL;DR: Production scale-up of high-purity diacetylated C18:1 sophorolipid lactone was demonstrated from lab to pilot scale with the Starmerella bombicola lactone esterase overexpression strain (oe sble) as production organism.
Abstract: Production scale-up of high-purity diacetylated C18:1 sophorolipid lactone was demonstrated from lab to pilot scale with the Starmerella bombicola lactone esterase overexpression strain (oe sble) as production organism. The 150 L fermentation using oleic acid and yeast extract, characterized by a titer of 199 g/L and a volumetric productivity of 0.9 g/L·h, was most successful in obtaining a highly pure (>98%) and uniform (96% C18:1 SL lactone) sophorolipid product suitable for chemical derivatization. The fermentation product was subsequently modified to produce sophorolipid amine oxides, which cannot be produced enzymatically. First, the fermentation product was transformed into an intermediate sophorolipid aldehyde via methanolysis and protection of the sugar head through acetylation and ozonolysis. This aldehyde intermediate was then used for the synthesis of the sophorolipid amine oxides via reductive amination, oxidation, and deprotection of the sugar head. The total yield of this synthetic pathway a...
TL;DR: 3-Imidoallenylphosphonates, allenes bearing both an electron-withdrawing and -donating group, were isolated for the first time and an alkoxy substituent was introduced into these unprecedented intermediates in a one-pot approach, yielding β-functionalized aminophosphonate in excellent yields and short reaction times.
TL;DR: In this paper, the influence of thermo-pressing conditions on the boards' mechanical properties, such as their thickness swelling and their water absorption, was evaluated, and the optimal board was molded at 200 °C temperature, 36.8 MPa pressure and 180 s time.
Abstract: New fiberboards were manufactured from a coriander cake through thermo-pressing, and the influence of thermo-pressing conditions (temperature, pressure and time) on the boards’ mechanical properties, their thickness swelling and their water absorption was evaluated. Because the protein glass transition systematically occurred during molding, this resulted in effective wetting of the fibers. Consequently, all boards were cohesive, with proteins and fibers acting as binder and reinforcing fillers, respectively. Flexural properties were influenced by all tested conditions, and the optimal board was molded at 200 °C temperature, 36.8 MPa pressure and 180 s time. Its flexural strength at break and its elastic modulus were 11.3 MPa and 2.6 GPa, respectively, with the highest surface hardness of the entire study. Simultaneously, thickness swelling and water absorption were low: 51% and 33%, respectively. This board would be applicable as pallet interlayer sheeting for the manufacture of containers or furniture or in the building trade.
TL;DR: A continuous-flow methodology was developed for the fast and selective synthesis of the otherwise highly unstable acryloyl chloride, mainly important for the acrylate and polymer industry.
Abstract: Acid chlorides are an important class of compounds and their high reactivity and instability has prompted us to develop a straightforward procedure for their synthesis with on-demand and on-site synthesis possibilities. The focus of this report is acryloyl chloride, mainly important for the acrylate and polymer industry. A continuous-flow methodology was developed for the fast and selective synthesis of the otherwise highly unstable acryloyl chloride. Three routes were investigated in a microreactor setup and all three can potentially be used for its production. The methodology was further expanded to the synthesis of other unstable acid chlorides by both the thionyl chloride and the oxalyl chloride mediated processes. The most sustainable method was the oxalyl chloride mediated procedure under solvent-free conditions, in which near-equimolar amounts of carboxylic acid and oxalyl chloride were used in the presence of catalytic amounts of DMF at room temperature. Within 1 to 3 min, nearly full conversions into the acid chlorides were achieved.
TL;DR: The synthesis and pharmaceutical properties of pyrrolopyrimidines have been summarized in this paper, where the authors present a review of recent literature on pyrrole-based scaffolds.
Abstract: This review summarizes recent literature (2000–2015) on the synthesis and pharmaceutical properties of pyrrolopyrimidines. These modified pyrimidine bases, fused to a pyrrole ring, and their corresponding nucleosides display a broad applicability in medicinal chemistry. This overview is divided into three main sections, according to the respective isomers: pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, and pyrrolo[3,4-d]pyrimidines. Each section contains a description of common retro-synthetic strategies, with particular attention for newly reported synthetic entries to the scaffold. Next, the synthetic strategies and the ways in which the scaffolds can be further modified are exemplified according to the biological properties of the obtained products.
TL;DR: The transfection results indicate that quaternary ammonium-based sophorolipids proved to be more efficient pDNA carriers than their deglycosylated counterparts and offer good potential for the development of new vectors for gene delivery based on renewable resources.
Abstract: Five quaternary ammonium amphiphilic compounds were synthesized from sophorolipid 1. These compounds were formulated in aqueous media and some of them (5 and 6) produced well-defined supramolecular aggregates which were characterized by DLS and zeta measurements. Their capacity to transfect four different eukaryotic cell lines in vitro was assessed. To evaluate the influence of the carbohydrate head group from the sophorolipids on the transfection efficacies, their deglycosylated analogues were also synthesized and tested for gene delivery. For all the compounds, the use of DOPE as a helper lipid in a 1:1 molar ratio with the ammonium-based lipids was required to obtain homogeneous formulations. The transfection results indicate that quaternary ammonium-based sophorolipids proved to be more efficient pDNA carriers than their deglycosylated counterparts. Moreover, the presence of the carbohydrate head group clearly contributed to the good biocompatibility of these cationic lipids. These cationic sophorolipid derivatives thus offer good potential for the development of new vectors for gene delivery based on renewable resources.
TL;DR: In the reactions of 1-aminoalkylphosphonic acids with other halogen-water reagents investigated by (31)P NMR, scission of the Cα-P bond was also observed, the reaction rates being comparable for bromine and chlorine, but much slower for iodine.
Abstract: The reactions of 1-aminoalkylphosphonic acids with bromine-water, chlorine-water and iodine-water were investigated. The formation of phosphoric(v) acid, as a result of a halogen-promoted cleavage of the Cα-P bond, accompanied by nitrogen release, was observed. The dephosphonylation of 1-aminoalkylphosphonic acids was found to occur quantitatively. In the reactions of 1-aminoalkylphosphonic acids with other halogen-water reagents investigated by (31)P NMR, scission of the Cα-P bond was also observed, the reaction rates being comparable for bromine and chlorine, but much slower for iodine.
TL;DR: In this paper, a review of the latest and most relevant developments in the field of continuous flow chemistry with the focus on hazardous reactions is presented, with the goal of making chemistry more accessible for laboratory and industrial applications.
Abstract: Over the last two decades, flow technologies have become increasingly popular in the field of organic chemistry, offering solutions for engineering and/or chemical problems. Flow reactors enhance the mass and heat transfer, resulting in rapid reaction mixing, and enable a precise control over the reaction parameters, increasing the overall process selectivity, efficiency and safety. These features allow chemists to tackle unexploited challenges in their work, with the ultimate objective making chemistry more accessible for laboratory and industrial applications, avoiding the need to store and handle toxic, reactive and explosive reagents. This review covers some of the latest and most relevant developments in the field of continuous flow chemistry with the focus on hazardous reactions.
TL;DR: In this article, isotope-labeled analogues of quorum sensing signal molecules belonging to the three major classes of naturally occurring N-acylated homoserine lactones (AHLs) with the label on a non-enolizable and therefore stable position were used for analysis via isotope dilution mass spectrometry.
Abstract: Aliphatic aldehydes were deuterated at the α-position via a base-catalyzed exchange reaction with D2O. These deuterated building blocks were used for the synthesis of labelled analogues of quorum sensing signal molecules belonging to the three major classes of naturally occurring N-acylated homoserine lactones (AHLs), with the label on a non-enolizable and therefore stable position. Besides the application of these stable isotope-labelled AHLs as a labelled standard for analysis via isotope dilution mass spectrometry, these compounds can be used to study the metabolic fate of the fatty acid tail of the AHL-molecule. These isotope-labelled compounds were fully characterized and used to synthesize the deuterated analogues of two commonly occurring AHL-degradation products, a tetramic acid and a ring opened N-acyl homoserine.
TL;DR: The significance of renewable resources within the chemical industry is constantly increasing as mentioned in this paper and they serve as alternatives for fossil resources whose supply is limited and who have a major impact on the environment.
Abstract: The significance of renewable resources within the chemical industry is constantly increasing. In the pursuit of sustainability, they serve as alternatives for fossil resources whose supply is limited and who have a major impact on the environment. Due to their complex structure and divergent biological activities, sophorolipids are interesting renewable resources. Unfortunately, industrial applications of natural sophorolipids are limited because of their high production cost. Therefore, chemical and enzymatic modifications provide an excellent tool to shift the application area of sophorolipids to high-added value sectors, in particular for the pharmaceutical sector. This review will give an overview of the modifications performed so far and their possible applications.
TL;DR: Although these structures have a great similarity with benzodiazepines, much less work has been published on their synthesis or derivatization, and there is a need to further develop these classes of underexplored scaffolds, in search for new chemistry, new methodology and hence new biological features.
Abstract: The immense amount of research on benzodiazepines resulted in the synthesis of heterocycle-fused diazepine derivatives with potential pharmacological activity. Pyridoazepines are recognized to be active in the central nervous system and have a comparable activity to the well-known benzodiazepines. This makes the synthesis and the study of pyridodiazepines an important research topic. This review comprises of the synthesis and activity of pyridodiazepines, pyridooxazepines and pyridothiazepines. Although these structures have a great similarity with benzodiazepines, much less work has been published on their synthesis or derivatization. Therefore, there is a need to further develop these classes of underexplored scaffolds, in search for new chemistry, new methodology and hence new biological features.
01 Jan 2016
TL;DR: In this article, a biphasic esterification method was proposed for short-chain carboxylic acid extraction and conversion to the higher value esters in a hydrophobic layer.
Abstract: Short-chain carboxylic acids are appealing targets for resource recovery because they are platform chemicals that can be produced from biomass, bio-waste or CO2 through anaerobic microbial conversion. Side streams that contain these feedstocks can be valorised as renewable carbon sources to added value products instead of being disposed. The microbial conversion and primary recovery through membrane electrolysis results in a clean acid stream with carboxylic acid concentrations below 100 g/L in the current state of the art. A further concentration and separation from this aqueous stream is required to use the acids as building blocks. This is however challenging due to the hydrophilicity, low titres and relatively low value of these compounds, which render conventional separation methods unattractive. The aim of this work is to address this separation bottleneck through biphasic esterification, i.e. a combined extraction and conversion to the higher value esters in a hydrophobic layer. Ionic liquids are appropriate compounds as hydrophobic layer because of their good solvating properties, high stability and their non-volatility, which facilitates separation of the higher volatile esters. The non-volatility results in a substantially reduced energy input compared to distillation, by avoiding energy loss as latent heat of the extractant. Ionic liquids furthermore have the ability to be tuned towards a specific application by combination of the anion and the cation; a compelling feature for extraction of relatively polar compounds into a hydrophobic layer. A proof of concept was successfully delivered in this exploratory study for the model compound acetic acid with a phosphonium ionic liquid, demonstrating it is possible to produce ethyl acetate from 100% renewable resources (biomass/CO2 and bio-ethanol) at reasonable rates and mild reaction conditions (atmospheric pressure, T ≤ 75°C). The development of a low-cost separation method for an integrated pipeline for the transformation of organic side streams to valuable bioproducts can provide competitive edge to the biosector.
TL;DR: In this paper, the authors present a survey of recent developments in this area related to the synthesis of heterocyclic compounds, including telescoping, in which several subsequent reaction steps (with or without purification) can be achieved by connecting different reactors to each other.
Abstract: Continuous microreactor systems have gained a lot of interest in the field of organic synthesis as these possess enhanced mass and heat transfer properties. Microreactor technology also offers a contemporary way of conducting chemical reactions in a more sustainable fashion due to the miniaturization and increased safety, and also in a technically improved manner due to intensified process efficiency. Recent developments in this area related to the synthesis of heterocyclic compounds are recorded in this chapter. Also, telescoping, in which several subsequent reaction steps (with or without purification) can be achieved by connecting different reactors to each other, is covered.
TL;DR: Starting from N-phthalimide protected phosphonylated propargylamine and various alcohols, a mild and efficient one-pot approach to β-substituted aminophosphonates via 3-imidoallenylphosphonate is elaborated.
Abstract: Starting from N-phthalimide protected phosphonylated propargylamine and various alcohols a mild and efficient one-pot approach to β-substituted aminophosphonates via 3-imidoallenylphosphonates is elaborated.