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DNA encoded library (DEL) synthesis represents a convenient means to produce, annotate and store large collections of compounds in a small volume. While DELs are well suited for drug discovery campaigns, the chemistry used in their production must be compatible with the DNA tag, which can limit compound class accessibility. As a result, most DELs are heavily populated with peptidomimetic and sp2‐rich molecules. Herein, we show that sp3‐rich mono‐ and bicyclic heterocycles can be made on DNA from ketochlorohydrin aldol products through a reductive amination and cyclization process. The resulting hydroxypyrrolidines possess structural features that are desirable for DELs and target a distinct region of pharmaceutically relevant chemical space. [ABSTRACT FROM AUTHOR]

This short review highlights the hitherto realised synthetic approaches towards organic 1,2-chlorohydrins by functionalisation of alkenes (i.e., 1,2-chlorohydroxylation), which is the most prominent access route to this class of compounds. Also, some other synthetic approaches involving the reduction of α-chloroketones, the epoxide opening ring by chloride anions and the utilisation of Grignard reagents for the synthesis of these compounds and chlorination of allylic alcohols are highlighted. Finally, enzymatic reactions for the formation of chlorohydrins are briefly summarised followed by a short view on natural products containing this moiety. 1 Introduction 2 Applications for the Synthesis of 1,2-Chlorohydrins 2.1 Chlorohydroxylation of Alkenes 2.2 Reduction of Chloroketones 2.3 Metalorganic Reagents 2.4 Epoxide Ring Opening 2.5 Chlorination of Allylic Alcohols 2.6 Biochemical Methods 2.7 Selected Applications in Natural Product Total Synthesis 3 Conclusion [ABSTRACT FROM AUTHOR]

Here we report the first total synthesis of the marine macrolide salarin C, a potent anticancer agent, and demonstrate the biomimetic oxidation-Wasserman rearrangement to access salarin A. This synthesis relies on L-proline catalysis to install a chlorohydrin function that masks the sensitive C16-C17 epoxide and potentially mimics the biosynthesis of these compounds where a related chlorohydrin may yield both THF- and epoxide-containing salarins. Additional and key features of the synthesis include (i) macrocycle formation via ring-closing metathesis, (ii) macrocyclic substrate-controlled epoxidation of the C12-C13 allylic alcohol, and (iii) a late-stage Julia-Kocienski olefination to install the side chain. Importantly, this work provides a platform for the synthesis of other salarins and analogues of these potentially important anticancer natural products.

( S )-Atenolol (( S )-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% enantiomeric excess ( ee ) with the use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. A catalytic amount of base was used in deprotonation of the phenol building block. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination to yield the final drug. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles. The overall yield of ( S )-atenolol was 9.9%, which will be further optimized.

DNA encoded library (DEL) synthesis represents a convenient means to produce, annotate and store large collections of compounds in a small volume. While DELs are well suited for drug discovery campaigns, the chemistry used in their production must be compatible with the DNA tag, which can limit compound class accessibility. As a result, most DELs are heavily populated with peptidomimetic and sp 2 -rich molecules. Herein, we show that sp 3 -rich mono- and bicyclic heterocycles can be made on DNA from ketochlorohydrin aldol products through a reductive amination and cyclization process. The resulting hydroxypyrrolidines possess structural features that are desirable for DELs and target a distinct region of pharmaceutically relevant chemical space., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Abstract Background The early prediction of the severity of acute pancreatitis still represents a challenge for clinicians. Experimental studies have revealed the generation of specific halogenated lipids, in particular oleic acid chlorohydrin, in the early stages of acute pancreatitis. We hypothesized that the levels of circulating oleic acid chlorohydrin might be a useful early prognostic biomarker in acute pancreatitis in humans. Methods In a prospective, multicenter cohort study, plasma samples collected within 24 h after presentation in the emergency room from 59 patients with acute pancreatitis and from 9 healthy subjects were assessed for oleic acid chlorohydrin levels. Results Pancreatitis was mild in 30 patients, moderately severe in 16 and severe in 13. Oleic acid chlorohydrin levels within 24 h after presentation were significantly higher in patients that later progressed to moderate and severe acute pancreatitis. Using 7.49 nM as the cutoff point, oleic acid chlorohydrin distinguished mild from moderately severe-to-severe pancreatitis with high sensitivity/specificity (96.6/90.0%) and positive/negative predictive values (90.3/96.4%). Using 32.40 nM as the cutoff value sensitivity, specificity, positive and negative predictive values were all 100% for severe acute pancreatitis. It was found to be a better prognostic marker than BISAP score, hematocrit at 48 h, SIRS at admission, persistent SIRS or C-reactive protein at 48 h. Conclusions Oleic acid chlorohydrin concentration in plasma is elevated in patients with acute pancreatitis on admission and correlates with a high degree with the final severity of the disease, indicating that it has potential to serve as an early prognostic marker for acute pancreatitis severity.

Potentiating neuritogenesis through pharmacological intervention might hold therapeutic promise in neurodegenerative disorders and acute brain injury. Here, we investigated the novel neuritogenic potentials of a steroidal chlorohydrin, 3β, 6β-dichloro-5-hydroxy-5α-cholestane (hereafter, SCH) and the change in cellular proteome to gain insight into the underlying mechanism of its neurotrophic activity in hippocampal neurons. Morphometric analysis showed that SCH promoted early neuronal differentiation, dendritic arborization and axonal maturation. Proteomic and bioinformatic analysis revealed that SCH induced upregulation of several proteins, including those associated with neuronal differentiation and development. Immunocytochemical data further indicates that SCH-treated neurons showed upregulation of Hnrnpa2b1 and Map1b, validating their proteomic profiles. In addition, a protein-protein interaction network analysis identified TrkA as a potential target connecting most of the upregulated proteins. The neurite outgrowth effect of SCH was suppressed by TrkA inhibitor, GW441756, verifying TrkA-dependent activity of SCH, which further supports the connection of TrkA with the upregulated proteins. Also, the computational analysis revealed that SCH interacts with the NGF-binding domain of TrkA through Phe327 and Asn355. Collectively, our findings provide evidence that SCH promotes neuronal development via upregulating TrkA-signaling proteins and suggest that SCH could be a promising therapeutic agent in the prevention and treatment of neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Abstract Polyamideamine-epichlorohydrin resin (PAE) is one of the most commonly used wet strength agents in the papermaking industry. However, adsorbable organic halogens (AOX) are known to be a toxic side product of the PAE manufacturing process; therefore, the use of PAE is restricted by regulation for food and medical applications. In this study, we investigated partially replacing the indirect food additive, PAE, with a renewable, biodegradable material, cellulose nanofibres (CNF), in order to drastically reduce the amount of PAE used while maintaining the same wet tensile strength. The concept is to replace covalent bonds by hydrogen bonds and to drastically increase bonding area. Depth-type filters were prepared with cellulose (30%), perlite (70%) and lesser amounts of PAE via papermaking technique. A small fraction of cellulose fibre composition was substituted with CNF while the PAE amount was gradually decreased. The substitution of positively charged PAE for negatively charged cellulose nanofibres switched the overall charge of the system from cationic to anionic. Therefore, two cationic polyelectrolytes, CPAM or PEI, were investigated to control the overall charge and adsorption performance of the filter system. The substitution of CNF enabled PAE dosage to be reduced by over 95% while retaining the wet strength properties of the filters. The wet strength obtained from the small quantity of wet strength polymer could be further improved by increasing the curing temperature to 150 °C with a much shorter curing period. The filters with reduced PAE dosage have also improved adsorption of positively charged contaminants. However, for negatively charged contaminants a very minor amount (around 20 mg/g) of cationic polymer addition would be required to maintain the performance. Our study shows that partial replacement of conventional papermaking fibres with cellulose nanofibres allows us to reduce the quantity of wet strength polymer remarkably and achieve a sustainable and environmentally-friendly concept for filter manufacturing or for any paper product requiring wet strength. Highlights • Cellulose fibre-perlite depth filters with varying compositions were developed. • PAE was replaced with CNF while maintaining the same wet strength properties. • CNF enabled PAE dosage to be reduced by over 95% while retaining the wet strength. • CPAM and PEI retained the charge characteristics successfully. • Small dosage of PEI drastically improved adsorption of anionic molecules. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A novel molecular probe (DMMA-IR780) which could show cross-channel color response was developed. • A High-throughput Smartphone-based Colorimetric Reader (HSCR) was designed and applied for signal recording. • An Android-based application was developed to realize convenient connection between HSCR and camera located in smartphone. • It provides a great potential for home test or on-site determination of HOCl in water. Abstract A high-throughput smartphone-based colorimetric reader (HSCR) was developed to quantitatively detect hypochlorite in aqueous solution and determine hypochlorite scavenging capacity in high-throughput format by a blue probe DMMA-IR780, which changes from deep blue to pink upon epoxidation by hypochlorite on one of the double bonds. The reaction mechanism between probe and hypochlorite was study by mass spectrum and attribute to the formation and degradation of chlorohydrins. The color change was recorded by a smartphone-based colorimetric reader to apply into an android-based application for on-site determination and analysis. This portable system could quantify hypochlorite with linearity range of 0.43 to 875 μM and limit of detection at 0.08 μM. Taking advantages of smartphone and probe DMMA-IR780, the assay provides a cost-effective and hand-held platform for on-site HOCl determination and quantification of hypochlorite scavenging capacity of dietary antioxidants. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Coupled fermentation-bioconversion process for the production of α-chlorohydrin. • High temperature fermentation process for the release of intracellular ketoreductase. • Conversion of 200 g/L α-chloroketone in heterogeneous reaction mixture and reuse of the enzyme. Abstract Enzymatic production of chemicals typically includes fermentation of engineered bacteria, preparation of enzymes, and bioconversion processes. Here coupled fermentation-bioconversion process for production of chiral atazanavir intermediate α-chlorohydrin was established. In the fermentation step, the ketoreductase was released from recombinant E. coli cells into medium after high-temperature induction, and the enzyme activity reached 5960 U/mL in the fermentation supernatant. In the bioconversion step, the fermentation supernatant was used directly for conversion of 200 g/L α-chloroketone in heterogeneous reaction mixture, and the residual amount of chloroketone reached less than 0.1% after 24 h of reaction. After filtration and drying, powder α-chlorohydrin was obtained with total yield of 95.7%. Finally, the filtrate of the reaction mixture was used for 2nd batch conversion, and powder α-chlorohydrin was obtained with yield of 95.6%. The above coupled process simplified enzyme preparation procedure, allowed the bioproduction of α-chlorohydrin to be carried out smoothly with reduced waste water discharge, and was advantageous for industrial scale-up. [ABSTRACT FROM AUTHOR]

Alkylation of DNA by 7r,8t-dihydroxy,9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) forms mainly trans adducts (with respect to the C-9/10 positions). We recently described a halide-catalyzed pathway that preferentially generates cis adducts and now report that the trans chlorohydrin of anti-BPDE (trans-BPDCH) is an intermediate in the chloride-catalyzed reaction. trans-BPDCH was synthesized, and both it and anti-BPDE were reacted with deoxyadenosine as a model DNA nucleophile. The stereochemistry and yields of deoxyadenosine adducts were determined as a function of chloride concentration. In the absence of salt, the fraction of cis adducts obtained from anti-BPDE and trans-BPDCH are 0.33 and 0.67, respectively. Adding sodium chloride increases the fraction of cis adducts (and consequently decreases the fraction of trans adducts), with the midpoint of the increase for both substrates at approximately 35-40 mM chloride. The chloride-dependent curves for BPDE and BPDCH converge at 1 M chloride, where the fraction of cis adducts is 0.88. Chloride also increases the total yield of cis adducts with either substrate, whereas the yield of trans adducts from the chlorohydrin is not significantly changed. These results support a mechanism by which chloride ion undergoes nucleophilic addition to the benzylic C-10 position of anti-BPDE. This generates a trans halohydrin that alkylates DNA with inversion of configuration to form a cis adduct. This pathway may have biological significance because chlorohydrins could form in serum or in cells with relatively high intracellular concentrations of chloride.

Crude glycerol (C3H8O3) is a major by-product of biodiesel production from vegetable oils and animal fats. The increased biodiesel production in the last two decades has forced glycerol production up and prices down. However, crude glycerol from biodiesel production is not of adequate purity for industrial uses, including food, cosmetics and pharmaceuticals. The purification process of crude glycerol to reach the quality standards required by industry is expensive and dificult. Novel uses for crude glycerol can reduce the price of biodiesel and make it an economical alternative to diesel. Moreover, novel uses may improve environmental impact, since crude glycerol disposal is expensive and dificult. Glycerol is a versatile molecule with many potential applications in fermentation processes and synthetic chemistry. It serves as a glucose substitute in microbial growth media and as a precursor in the synthesis of a number of commercial intermediates or fine chemicals. Chlorinated derivatives of glycerol are an important class of such chemicals. The main focus of this review is the conversion of glycerol to chlorinated derivatives, such as epichlorohydrin and chlorohydrins, and their further use in the synthesis of additional downstream products. Downstream products include non-cyclic compounds with allyl, nitrile, azide and other functional groups, as well as oxazolidinones and triazoles, which are cyclic compounds derived from ephichlorohydrin and chlorohydrins. The polymers and ionic liquids, which use glycerol as an initial building block, are highlighted, as well.

Abstract Chiral chlorohydrins are used as intermediates in the synthesis of various compounds with biological activities. This paper reports the synthesis of α-chloroketones 2a–c with oxone® and NH 4 Cl at reflux via 30 min of exposure to microwave irradiation and conventional heating, in situ, followed by reduction with whole cells of marine-derived fungi (Penicillium citrinum CBMAI 1186, Mucor racemosus CBMAI 847, Aspergillus sydowii CBMAI 935, Penicillium raistrickii CBMAI 931, and Penicillium oxalicum CBMAI 1185), yielding the respective chlorohydrins 3a–c with good conversion (32–97%) and enantioselectivities (60–94%). This is the first study involving the synthesis of α-chlorophenones in situ followed by biocatalytic reduction from whole cells of marine-derived fungi to obtain enantio-enriched chlorohydrins 3a–c. Graphical abstract fx1 Highlights • Synthesis of α-chloroketones with oxone® and NH 4 Cl under microwave irradiation and conventional heating. • Synthesis of α-chlorophenones in situ followed by biocatalytic reduction. • Fungi marine used in the obtaining of chiral chlorohydrins. [ABSTRACT FROM AUTHOR]

Reaction of styrene with chlorine dioxide under various conditions selectively produces 1-phenyl- 2-chloroethanone, with 1-phenyl-2-chloroethanol, 2-hydroxy-1-phenylethanone, (1,2-dichloroethyl)benzene, (2-chloro-1-phenyl)ethene, and (1,2,2-trichloroethyl)benzene isolated as reaction byproducts. [ABSTRACT FROM AUTHOR]

A short enantioselective total synthesis of 1-deoxygalactonojirimycin (migalastat) has been achieved that does not rely on chiral pool starting materials or biocatalysis. Instead, this synthesis exploits a one-pot proline-catalyzed α-chlorination and aldol reaction of a commercially available aldehyde to assemble the entire carbon skeleton in a single step. The key role played by a nitrogen protecting group in the final epoxide opening reaction is highlighted as is the amenability to access structural analogues using this route. [ABSTRACT FROM AUTHOR]

Background: The early prediction of the severity of acute pancreatitis still represents a challenge for clinicians. Experimental studies have revealed the generation of specific halogenated lipids, in particular oleic acid chlorohydrin, in the early stages of acute pancreatitis. We hypothesized that the levels of circulating oleic acid chlorohydrin might be a useful early prognostic biomarker in acute pancreatitis in humans. Methods: In a prospective, multicenter cohort study, plasma samples collected within 24 h after presentation in the emergency room from 59 patients with acute pancreatitis and from 9 healthy subjects were assessed for oleic acid chlorohydrin levels. Results: Pancreatitis was mild in 30 patients, moderately severe in 16 and severe in 13. Oleic acid chlorohydrin levels within 24 h after presentation were significantly higher in patients that later progressed to moderate and severe acute pancreatitis. Using 7.49 nM as the cutoff point, oleic acid chlorohydrin distinguished mild from moderately severe-to-severe pancreatitis with high sensitivity/specificity (96.6/90.0%) and positive/negative predictive values (90.3/96.4%). Using 32.40 nM as the cutoff value sensitivity, specificity, positive and negative predictive values were all 100% for severe acute pancreatitis. It was found to be a better prognostic marker than BISAP score, hematocrit at 48 h, SIRS at admission, persistent SIRS or C-reactive protein at 48 h. Conclusions: Oleic acid chlorohydrin concentration in plasma is elevated in patients with acute pancreatitis on admission and correlates with a high degree with the final severity of the disease, indicating that it has potential to serve as an early prognostic marker for acute pancreatitis severity. [ABSTRACT FROM AUTHOR]

A metal-free protocol for the selective cleavage of unstrained C–C single bonds was developed. Under the catalysis of KI and in the presence of NaHCO3, the readily available α -chloro- β -hydroxy ketones underwent bond breaking and sulfonylation smoothly to afford β -ketosulfones with high efficiency and broad substrate scope. Mechanism investigations, both experimental and theoretical, showed that a retro-aldol cleavage/nucleophilic substitution sequence might be involved. [ABSTRACT FROM AUTHOR]

Industrial production of dichloropropanols through chlorohydrination of allyl chloride suffers from a series of disadvantages such as use of hazardous Cl 2 , low atom economy, low dichloropropanol concentration and serious pollution. In this work, a safer and greener route for chlorohydrination of allyl chloride with H 2 O 2 and HCl over hollow titanium silicate (HTS) at mild condition is developed. Unlike the traditional Cl 2 -based chlorohydrination, this novel method is initiated via synergistic effect of Lewis acidity (HTS) and Brønsted acidity (HCl) to promote occurrence of oxidation, protonation and nucleophilic reaction of allyl chloride simultaneously and hence dichloropropanols are generated. Owing to a completely different reaction route, the formation of 1,2,3-trichloropropane by-product is depressed and the content of dichloropropanol exceeded 22 wt%, which increase by about 4 times compared with traditional Cl 2 -based chlorohydrination (the content of dichloropropanol is below 4 wt%). At the optimized conditions, both of the allyl chloride conversion and dichloropropanol selectivity could approach 99% simultaneously and the waste is minimized. What’s more, the HTS was reusable. Concentrated HCl solution treatment was adopted to test HTS’s stability. The characterization and catalytic evaluation results reveal that, although parts of the framework Ti species have transformed into non-framework Ti and then leached into the solution, HTS remains structural stable, and the allyl chloride conversion and dichloropropanol selectivity didn’t decrease obviously during the treatment. [ABSTRACT FROM AUTHOR]

A novel polyamidoaminoepichlorohydrin resin was prepared and analyzed using spectroscopy techniques and its anti-corrosion properties were studied and observed. Inhibition efficiency was calculated by impedance spectroscopy, loss in weight and potentiodynamic polarization. Authors inferred results as the inhibitors tested differently are acted as better anti-corrosive agent. The thermodynamic data of activation were determined. The adsorption of resin on the steel surface was calculated according to Langmuir adsorption theory. A surface study was performed using SEM, AFM, FT-IR and XRD. Inhibition mechanism was deduced from concentration and temperature dependence of inhibition efficiency, Langmuir adsorption, SEM and AFM results. [ABSTRACT FROM AUTHOR]

The ring opening of steroidal epoxides are carried out in a regioselective manner using bismuth chloride, ferric chloride, indium chloride, silica supported BiCl 3 , FeCl 3 and InCl 3 under mild condition in variable yields. The products obtained were identified by various spectroscopic techniques. The structure of one of the compound has been determined by X-ray diffraction using the direct method and was refined on F2 by the full-matrix least-squares. A general mechanistic scheme for the reaction is proposed on the basis of current and previous results and the mode of epoxide ring-opening. The 3D Hirshfeld surfaces and the associated 2D fingerprint plots were also drawn in order to explore plausible intermolecular interactions. The fingerprint plots evidenced subtle distinctions in the intermolecular contacts for the independent molecules. [ABSTRACT FROM AUTHOR]

An analytical strategy based on a hybrid quadrupole-Orbitrap mass spectrometry was proposed for the simultaneous screening of known destruxins and characterization of potential members of this class of secondary metabolites, in order to evaluate the metabolite production of entomopathogenic fungi used as biocontrol agents. Initially, the fragmentation pathway of the known and commercially available destruxin A was established combining high resolution mass spectrometry (HRMS) and multiple stage MS data in order to obtain the strategy for the characterization of other destruxins for which reference standards were not available. Nineteen known destruxins including A, B, C, D, Ed, F, A, B, Ed, A, B, D, A, DesmA, DesmB, DesmC, DesmB, and two chloro-derivatives (Cl and E chlorohydrin) were unequivocally identified in Metarhizium brunneum using the proposed strategy. In addition, four unknown destruxins, namely C, Ed, G, and G, were structurally elucidated and characterized for the first time in this fungal strain. [ABSTRACT FROM AUTHOR]

Artificial enzymes are required to catalyse non-natural reactions. Here, a hybrid catalyst was developed by embedding a novel Ru complex in the transport protein NikA. The protein scaffold activates the bound Ru complex to produce a catalyst with high regio- and stereo-selectivity. The hybrid efficiently and stably produced α-hydroxy-β-chloro chlorohydrins from alkenes (up to 180 TON with a TOF of 1050 h−1). [ABSTRACT FROM AUTHOR]

Lignin derivative vanillin when coupled with diamines and diethyl phosphite followed by reaction with echichlorohydrin yields high-performance flame retardant epoxy resins. Biorenewable and environment-friendly flame retardant alternatives to bisphenol A epoxy resins (having plenty of applications such as coatings, adhesives, composites, etc.) have captured great attention due to their ecological and economic necessity. Vanillin, an industrial scale monoaromatic compound from lignin, is a promising sustainable candidate for high-performance polymers, while synthesis of diepoxies is challenging. Meanwhile, bio-based epoxy resins combining high performance and excellent fire resistance are more difficult to be achieved. In this paper, two novel bio-based epoxy monomers EP1 and EP2 were synthesized by one-pot reaction containing Schiff base formation and phosphorus-hydrogen addition between vanillin, diamines, and diethyl phosphite, followed by reacting with epichlorohydrin. Their reactivities are similar to bisphenol A epoxy resin DGEBA. After curing they showed excellent flame retardancy with UL-94 V0 rating and high LOI of ∼32.8%, which was due to the outstanding intumescent and dense char formation ability. Meanwhile, it was found that the cured vanillin-based epoxies had exceedingly high Tgs of ∼214°C, tensile strength of ∼80.3 MPa, and tensile modulus of ∼2709 MPa, much higher than the cured DGEBA with Tg of 166°C, tensile strength of 76.4 MPa, and tensile modulus of 1893 MPa; the properties of vanillin-based epoxies are easy to be regulated by using different "coupling" agents diamines during the synthesis process. [ABSTRACT FROM AUTHOR]

Chlorine is a widely available toxic chemical that has been repeatedly used in armed conflict globally. The Organization for the Prohibition of Chemical Weapons (OPCW) have on numerous occasions found "compelling confirmation" that chlorine gas has been used against civilians in northern Syria. However, currently, there are no analytical methods available to unambiguously prove chlorine gas exposure. In this study, we describe the screening for chlorinated biomolecules by the use of mass isotope ratio filters followed by the identification of two biomarkers present in bronchoalveolar lavage fluid (BALF) from chlorine gas exposed mice. The relevance of these markers for human exposure was verified by their presence in in vitro chlorinated human BALF. The biomarkers were detectable for 72 h after exposure and were absent in nonexposed control animals. Furthermore, the biomarkers were not detected in humans diagnosed with chronic respiratory diseases. The potential chlorine specific markers were all chlorohydrins of unsaturated pulmonary surfactant phospholipids; phosphatidylglycerols, and phosphatidylcholines. Mass spectrometry fragmentation characteristics were favorable for the phosphatidylglycerol chlorohydrins, and they were therefore proposed as the best biomarker candidates. [ABSTRACT FROM AUTHOR]

Microbial transformation of 6-dehydroprogesterone ( 1 ) with Aspergillus niger yielded three new metabolites, including 6 β -chloro-7 α ,11 α -dihydroxypregna-4-ene-3,20-dione ( 2 ), 7 α -chloro-6 β ,11 α -dihydroxypregna-4-ene-3,20-dione ( 3 ), and 6 α ,7 α -epoxy-11 α -hydroxypregna-4-ene-3,20-dione ( 4 ), and two known metabolites; 6 α ,7 α -epoxypregna-4-ene-3,20-dione ( 5 ), and 11 α -hydroxypregna-4,6-diene-3,20-dione ( 6 ). Compounds 2 , and 3 contain chlorohydrin moiety at C-6, and C-7, respectively. The biotransformation of 1 with Gibberella fujikuroi yielded a known compound, 11 α ,17 β -dihydroxyandrosta-4,6-dien-3-one ( 7 ). [ABSTRACT FROM AUTHOR]

3-Chloroquinoline-2,4-diones were reduced with sodium borohydride to give syn - and anti -chlorohydrins, the stereochemistry of which was established by NMR spectroscopy. Both stereoisomeric chlorohydrins were reacted with potassium carbonate in methanol. anti -Isomers afforded the corresponding epoxides or rearranged to 3-hydroxy-4-alkylquinolin-2-ones, whereas syn -isomers did not react. However, these isomers converted to 4-hydroxyquinolin-2-ones after standing for a long period of time in DMSO. After reaction with thionyl chloride, the syn -isomers yielded cis - and trans -3,4-dichloroquinolin-2-ones. [ABSTRACT FROM AUTHOR]

Steam distillation was applied to lampante olive oil and olive pomace oil in a laboratory-scale steam distillation equipment, and effects of process parameters (temperature, pressure and stripping steam) were determined and modeled on bound 3-MCPD and glycidyl ester formation. Levels of process parameters were optimized to minimize bound 3-MCPD and glycidyl ester formation using response surface methodology. According to the results of the study, olive pomace oil has a significant content (4.1 mg/kg) of bound 3-MCPD prior to steam distillation. Results showed that temperature of the steam distillation was highly effective on bound 3-MCPD and glycidyl ester formation. Interaction between stripping steam rate and temperature was statistically significant for glycidyl ester formation. Effects of process parameters were visualized by using perturbation plots. Perturbation plots showed that stripping steam rate was possibly effective not only on glycidyl ester formation, but also on bound 3-MCPD formation in the case of steam distillation carried out at wide-ranged process conditions. According to the optimization results, optimum steam distillation temperature is 230 °C, water flow rate is 1.2 ml/min, and pressure is 4 mbar for olive oil, and temperature is 230 °C, water flow rate is 1 ml/min, and pressure is 2 mbar for olive pomace oil to minimize the bound 3-MCPD and glycidyl ester formation. [ABSTRACT FROM AUTHOR]

A new sensitive method for the indirect determination of ester-bound 2,3-dichloro-1-propanol (2,3-DCP), 1,3-dichloro-2-propanol (1,3-DCP), 2-chloro-1,3-propanediol (2-MCPD), 3-chloro-1,2-propanediol (3-MCPD) and 2,3-epoxy-1-propanol (glycidol) in oil matrices is presented. It is based on a mild alkaline-catalysed release of chlorohydrins and glycidol, followed by a transformation of glycidol to monobromopropanediol (MBPD) according to a modification of the AOCS Official Method Cd 29b-13 (3-in-1 method). The dichloropropanols are separated from the monohalogenated diols and the oil matrix by l/l extraction and determined separately by headspace gas chromatography-mass spectrometry (GC-MS-HS). Both MCPD isomers and the glycidol derivative are derivatised with phenylboronic acid (PBA) and analysed by GC-MS separately. Method validation was performed in an oil matrix using isotopic labelled esterified standards. Linearity was verified for all analytes ( r2 > 0.998). The limit of detection (LOD) for all analytes was ≤5 μg/kg. The modified determination of ester-bound MCPD and glycidol was tested for accuracy by analysing reference samples. All free and bound analytes were investigated regarding their stability against undesired alkaline-induced transformation. It was also demonstrated that bound MCPD and bound DCP might be generated in oil by heat treatment in the presence of a strong chloride donor. The method was applied to the analysis of a variety of different edible oils. None of the two tested dichloropropanols was detected. By contrast and as might be expected, both bound MCPD and bound glycidol were consistently detected in refined oils. Practical applications: The presented application is suitable for the parallel determination of ester-bound dichloropropanols and monochloropropanols and ester-bound glycidol in edible oils and fats using simple techniques for sample preparation. It covers more analytes and is more sensitive than other previously reported methods. Substitution of the double sample preparation, (a part of the AOCS Official Method Cd 29b-13), by determining a correction factor for a whole set of samples, may reduce the effort required for sample preparation and raw data analysis. Furthermore, the investigation of basic transformations that may occur during sample preparation can be helpful for a better understanding of the complex chemistry in MCPD and glycidol analysis. Similarly, the results from heating frying fat in the presence of aluminium chloride might help to understand the distribution of chlorohydrin isomers in heat-treated oils and fats. Assumed heat-induced formation pathways of ester-bound chlorohydrins in an edible oil. [ABSTRACT FROM AUTHOR]

We have explored the combination of ohmic heating (ΩH) with ionic liquids for indium-promoted reactions and report herein the indium-promoted dehalogenation of gem-dibromo alkenes and the indium-mediated reductive elimination of chlorohydrins for the synthesis of 1-halo alkenyl derivatives. Heck, Stille, Suzuki, Kumada and Sonogashira couplings of the resulting 1-halo-1-alkenes with appropriate reagents were carried out to give alkenes, dienes and enynes. [ABSTRACT FROM AUTHOR]

The benefits and deficiencies of several methods of analysis for PPO and PXH, including the aqueous extraction used in ASTA method 23.1 and the MTBE extraction method previously reported by the authors, will be discussed. Novel methods utilizing dynamic headspace extraction and solid phase microextraction (SPME) will also be reported with particular emphasis on preventing artefactual effects. Preliminary experiments have found that dynamic headspace sampling can lower detection limits by up to 3 orders of magnitude. [ABSTRACT FROM AUTHOR]

Epoxide ring opening is a frequently required transformation in Organic Synthesis. In this paper we describe the application of NbCl5 for this purpose using three different substrates. Chlorohydrins, 1,2-diols, products containing solvent residues as well as rearrangement products are obtained, depending on both the substrate structure and reaction conditions. Rationalizations to account for some of the results are suggested.

The total synthesis of the marine fungus-derived natural product ascospiroketal is described. This concise synthesis relies on a unique AgI-promoted tandem cascade cyclization that provides direct access to the correctly configured tricyclic core of the natural product from a linear precursor. The synthesis of candidate stereostructures of ascospiroketal A allowed for the confident assignment of both the relative and absolute stereochemistry of this unusual octaketide. [ABSTRACT FROM AUTHOR]

Six new naturally occurring polyoxygenated cyclohexene derivatives together with eight related known derivatives, two known alkaloids, and two known flavonoid derivatives were isolated from bioassay-guided fractionation of the ethyl acetate extract of the leaves and twigs of Dasymaschalon sootepense . The structure elucidation and determination of absolute configurations were established by various spectroscopic methods, X-ray diffraction techniques as well as comparison with the literature data. Several isolated compounds were evaluated for their cytotoxic, anti-HIV-1 RT and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

A Darzens reaction between tert-butoxycarbonyl alaninal and chloromethyl phenyl sulfone afforded chlorohydrins, which were converted into epoxysulfones by reaction with sodium tert-butoxide. Epoxysulfone 10 and chloroketone 14 derived from chlorohydrins by oxidation proved to be inhibitors of cathepsins H, S, and C as determined by competitive activity-based protein profiling. [ABSTRACT FROM AUTHOR]