Total synthesis of (+)-bongkrekic acid

Total synthesis of bongkrekic acid, an important apoptosis inhibitor, has been accomplished. The strategy includes inexpensive starting materials, asymmetric alkylation, anionic allyl coupling and oxidative manipulations. This process would provide a sufficient amount of bongkrekic acid and its analogues.     

超高效液相色谱-串联质谱法快速测定六神曲中的米酵菌酸

基于超高效液相色谱-串联质谱法（UPLC-MS/MS），建立了快速测定六神曲中生物毒素米酵菌酸残留的检测方法。样品首先以甲醇作为提取溶剂进行超声提取，再用氨水调节pH值至8，过滤，滤液用Oasis MAX强阴离子交换固相萃取柱处理。采用Waters HSS T3色谱柱（100 mm×2.1 mm，1.8 μm）分离，以乙腈-含0.1%（体积分数）甲酸的10 mmoL/L甲酸铵溶液为流动相，采用电喷雾电离（ESI）源电离，电离模式为负离子模式，质谱检测模式为多反应监测（MRM）模式。在最佳条件下，米酵菌酸在0.5~100 μg/L范围内呈良好的线性关系，相关系数（R²）>0.99。方法的加标回收率为80.6%~85.3%，日内和日间精密度分别为4.2%~6.8%和8.2%~13.2%。方法的检出限（LOD，S/N=3）和定量限（LOQ，S/N=10）分别为0.4 μg/kg和1.2 μg/kg。实际样品测定中发现了六神曲中存在米酵菌酸残留的现象，为保健食品和中药材中生物毒素的风险监控提供了重要的科技支撑。该方法简单、快速、灵敏度高，适用于六神曲中生物毒素米酵菌酸残留量的测定。     

Elucidation of the chemical structure of bongkrekic acid—I Isolation, purification and properties of bongkrekic acid

The preparation, isolation and purification of the toxic antibiotic bongkrekic acid (BA), produced by Pseudomonas cocovenenans on partially defatted coconut are described. It has been shown that BA is a branched unsaturated tricarboxylic acid with a gross formula of C₂₈H₃₈O₇. The presence of three methyl groups, one methoxyl group, one ring system and six double bonds—two isolated and two pairs of conjugated double bonds, both conjugated with a carboxyl group—is proved.     

The structure of bongkrekic acid

From NMR and MS studies, a new structure is proposed for the toxic antibiotic bongkrekic acid (BA), which is given by the formula: 3-carboxymethyl-17-methoxy-6,18,21-trimethyldocosa-2,4,8,12,14,18,20-heptaenedioic acid.     

Efficient synthesis of bongkrekic acid. Three-component convergent strategy

An efficient total synthesis of the apoptosis inhibitor bongkrekic acid was accomplished using a three-component convergent strategy involving a Kocienski-Julia olefination and a Suzuki-Miyaura coupling, in which the longest linear sequence was 18 steps and proceeded in 6.4% overall yield. The torquoselective olefination also contributed to the shortening of the synthesis.     

Simultaneous determination of toxic metabolites by linear combination derivative spectrophotometry.

A linear combination derivative spectrophotometric method is described. The method overcomes the problem of overlapping in derivative spectrophotometry and allows the maximum use of quantitative information. In addition, the method can be used to increase the selectivity, sensitivity and accuracy of the simultaneous analysis of multicomponent mixtures. The application of the method to the simultaneous determination of bongkrekic acid and toxoflavin, the toxic metabolites produced by Pseudomonas farinofermentans, is described.     

A Convenient One-Step Synthesis of 2-Hydroxy-1,3,5-Benzenetricarbaldehyde

The hexamethylenetetramine/trifluoroacetic acid system was demonstrated to be capable of introducing three aldehyde groups into the phenol molecule. Facile, one-step procedures were developed for the preparation of hitherto difficult to synthesize 2-hydroxy-1,3,5-benzenetricarbaldehyde starting from either phenol or 4-hydroxybenzaldehyde. New pKa measurements showed 2-hydroxy-1,3,5-benzenetricarbaldehyde to be an acid stronger than previously reported.     

Über Rosmarin und Rosmarinsäure

Rosmarinic acid, a tan from Lamiaceae, is found in rosemary and many other plants such as thyme, painted nettle, savory, sage, oregano, or lemon balm, from which it has been isolated here. It is a caffeic acid ester and a chiral, aromatic natural product. Rosmarinic acid tastes bitter, which may be attractive for rosemary as spice. Due to the catechol subunit the acid is an antioxidant. Using rosmarinic acid as a cure is possible due to manyfold physiological effects which are still under investigation. The rosmarinic acid biosynthesis pathway was completely elucidated at the painted nettle. This led to attempts to produce the acid biotechnologically by plant cell cultures in high yields. The preparation of a spectroscopically pure sample is challenging. All analytical spectra were recorded and are reproduced and interpreted either in the main part or in the supporting information.     

A Practical Synthesis of β-Keto Phosphonates from Triethyl Phosphonoacetate

An efficient and practical preparation of β-keto phosphonates, via acylation reaction of triethyl phosphonoacetate with carboxylic acid chlorides in the presence of magnesium chloride-triethylamine followed by decarbethoxylation, is described.     

Biosynthesis of the Respiratory Toxin Bongkrekic Acid in the Pathogenic Bacterium Burkholderia gladioli

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Highlights? Molecular basis for the biosynthesis of a fatal food toxin revealed ? Functional genetics by λ Red recombination in the pathogen Burkholderia gladioli ? Stereochemistry of modular bongkrekic acid PKS decoded ? β-Branching and six-electron methyl oxidation lead to tricarboxylic fatty acid     

Fragmentation characteristics of peptide-metal ion adducts under matrix-assisted laser desorption/ionization post-source decay time-of-flight mass spectrometric conditions

Fragmentation reactions of sodium-cationized enkephalin peptides generated by matrix-assisted laser desorption/ionization were studied using post-source decay (PSD) with a reflectron time-of-flight mass spectrometer. Several matrices and analyte-matrix sample preparation methods were evaluated for high-intensity ion currents that could last for the entire PSD analysis. A triple dried-droplet sample preparation procedure with 2,5-dihydroxybenzoic acid as the matrix was found to yield abundant longer-lasting ion signals of the peptide-Na(+) ion adducts. The principal decay product of these adduct ions is the [b(n-1) + Na + OH](+) ion, which provides an unambiguous identification of the C-terminal residue of a peptide. In some peptides, the loss of a second residue from the C-terminus is also observed. No other sequence-specific ions were observed.     

Novel Synthetic Method for Muscone

Muscone is a precious fragrant compound scarce in nature. Many attempts to synthesize this unique natural product have been carried out. In this work, a novel synthetic method for the preparation of muscone from 3‐methyl‐15‐hydroxypentadecanoate is provided. Benzimidazolium salt was used as tetrahydrofolate coenzyme model at formic acid oxidation level and Grignard reagent as nucleophile to which a one‐carbon unit was transferred. The biomimetic synthesis of muscone was successfully accomplished using the addition‐hydrolysis reaction of benzimidazolium salt with the Grignard reagent.     

One‐Pot Syntheses of 2‐(2‐Sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic Acid Derivatives via Reactions of 3‐(2‐Isothiocyanatophenyl)prop‐2‐enoic Acid Derivatives with Thiols or Sodium Sulfide

Two efficient methods for the preparation of 2‐(2‐sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid derivatives 3 under mild conditions have been developed. The first method is based on the reaction of 3‐(2‐isothiocyanatophenyl)prop‐2‐enoates 1a – 1c with thiols in the presence of Et₃N in THF at room temperature, leading to the corresponding dithiocarbamate intermediates 2 , which underwent spontaneous cyclization at the same temperature by an attack of the S‐atom at the prop‐2‐enoyl moiety in a 1,4‐addition manner (Michael addition) to give 2‐(2‐sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetates in one pot. The second method involves treatment of 3‐(2‐isothiocyanatophenyl)prop‐2‐enoic acid derivatives 1b – 1d with Na₂S leading to the formation of 2‐(2‐sodiosulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid intermediates 5 by a similar addition/cyclization sequence, which are then allowed to react with alkyl or aryl halides to afford derivatives 3 . 2‐(2‐Thioxo‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid derivatives 6 can be obtained by omitting the addition of halides.     

A green and efficient protocol for large‐scale production of glycyrrhizic acid from licorice roots by combination of polyamide and macroporous resin adsorbent chromatography

A green and efficient method for large‐scale preparation of glycyrrhizic acid from licorice roots was developed by combination of polyamide and macroporous resin. The entire preparation procedure consisted of two simple separation steps. The first step is to use polyamide resin to remove licorice flavoniods from the licorice crude extract. Subsequently, various macroporous resins were tried to purify glycyrrhizic acid, and HPD‐400 showed the most suitable adsorption and desorption properties. Under the optimized conditions, a large‐scale preparation of glycyrrhizic acid from licorice roots was carried out. A 20 kg raw material produced 0.43 kg of glycyrrhizic acid using green aqueous ethanol as the solvent. The purity of glycyrrhizic acid was increased from 11.40 to 88.95% with a recovery of 76.53%. The proposed method may be also extended to produce large‐scale other triterpenoid saponins from herbal materials.     

One‐Pot Synthesis of 2‐Substituted 4‐Aryl‐4,5‐dihydro‐3,1‐benzoxazepines from 2‐(2‐Aminophenyl)‐1‐arylethanols via Dehydration of the Corresponding Amides

An efficient method for the preparation of 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepine derivatives under mild conditions has been developed. The reaction of 2‐(2‐aminophenyl)ethanols 1 with acid chlorides in the presence of excess Et₃N in THF at room temperature gave the corresponding N‐acylated intermediates 2 , which were dehydrated by treatment with POCl₃ to give 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepines 3 in a one‐pot reaction.     

The effect of citric acid on the catalytic activity of nano‐sized MoS2 toward sulfur‐resistant CO methanation

In this work, a facile hydrothermal route was used to prepare nano‐sized MoS₂ catalyst. The effect of citric acid during the MoS₂ preparation process on the catalytic activity of sulfur‐resistant CO methanation was investigated. It was found that citric acid played an adverse role on the catalytic activity of MoS₂ toward sulfur‐resistant CO methanation. However, CO methanation performance turned out to be better when NH₂OH?HCl as a reductant was removed during the catalyst preparation process. The X‐ray diffraction (XRD) and infrared spectroscopy (IR) were performed to discuss the possible mechanism for the effect of citric acid towards CO methanation performance.     

Sulfated Carbon Quantum Dots as Efficient Visible‐Light Switchable Acid Catalysts for Room‐Temperature Ring‐Opening Reactions

Acid catalytic processes play a classic and important role in modern organic synthesis. How well the acid can be controlled often plays the key role in the controllable synthesis of the products with high conversion yield and selectivity. The preparation of a novel, photo‐switchable solid‐acid catalyst based on carbon quantum dots is described. The carbon quantum dots are decorated with small amounts of hydrogensulfate groups and thus exhibit a photogenerated acidity that produces a highly efficient acid catalysis of the ring opening of epoxides with methanol and other primary alcohols. This reversible, light‐switchable acidity is shown to be due to photoexcitation and charge separation in the carbon quantum dots, which create an electron withdrawing effect from the acidic groups. The catalyst is easily separated by filtration, and we demonstrate multiple cycles of its recovery and reuse.     

Polymer‐based monolithic column with incorporated chiral metal–organic framework for enantioseparation of methyl phenyl sulfoxide using nano‐liquid chromatography

A new approach to the preparation of enantioselective porous polymer monolithic columns with incorporated chiral metal–organic framework for nano‐liquid chromatography has been developed. While no enantioseparation was achieved with monolithic poly(4‐vinylpyridine‐co‐ethylene dimethacrylate) column, excellent separations of both enantiomers of (±)‐methyl phenyl sulfoxide were achieved with its counterpart prepared after admixing metal–organic framework [Zn₂(benzene dicarboxylate)(l‐lactic acid)(dmf)], which is synthesized from zinc nitrate, l ‐lactic acid, and benzene dicarboxylic acid in the polymerization mixture. These novel monolithic columns combined selectivity of the chiral framework with the excellent hydrodynamic properties of polymer monoliths, may provide a great impact on future studies in the field of chiral analysis by liquid chromatography.     

Facile Preparation of a Stable Fe3O4@LDH@NiB Magnetic Core‐Shell Nanocomposite for Hydrogenation

A novel NiB deposited layered double hydroxide (LDH ) coated ferroferric oxide (Fe₃O₄ @LDH @NiB ) magnetic core‐shell nanocomposite was successfully fabricated by the combination of coprecipitation and impregnation‐reduction. During the Fe₃O₄ @LDH preparation, a facile template‐free approach was employed to introduce the LDH shell, which was more efficient than the conventional method for the preparation of mesoporous materials that always needs to introduce and remove templates. The resulted Fe₃O₄ @LDH has a relatively high surface area and abundant surface hydroxyl group, which can adsorb metal ions, making it favorable to disperse and stabilize the active Ni species, as demonstraed by TEM , XPS , FT‐IR and BET characterizations. Therefore, it exhibited good activity in the selective hydrogenation of cinnamic acid to hydrocinnamic acid with the conversion and selectivity both approaching to 100%. Notably, the obtained Fe₃O₄ @LDH @NiB can be easily separated by an external magnetic field and recycled eleven times without appreciable loss of its initial catalytic activity.     

Safer Conditions for the Curtius Rearrangement of 1,3,5‐Benzenetricarboxylic Acid

A rapid method to prepare 1,3,5‐triaminobenzene and its derivatives is the tris‐Curtius rearrangment of 1,3,5‐benzenetricarboxylic acid. The hazards associated with the acyl azide route are minimized by using 1,2‐dichloroethane as solvent. A second method that avoids acyl azide preparation uses diphenylphosphoryl azide to yield the tricarbamate in one step.