Horseradish peroxidase-catalyzed polymerization of<Emphasis Type="Italic"> p</Emphasis>-hydroxycinnamic acid for synthesis of reactive microspheres

In this article, we report the experimental synthesis of reactive polymer microspheres of poly(p-hydroxycinnamic acid). Enzyme-catalyzed polymerization of poly(p-hydroxycinnamic acid) using horseradish peroxidase as a catalyst and hydrogen peroxide as an oxidant took place in a mixture solution of methanol and phosphate buffer solution; it was found that the fraction of methanol in the mixture solution strongly affected the yield of powdery polymer materials. The chemical structure of the polymers was characterized by ¹H-NMR and FT-IR spectroscopies, and the molecular weight was measured by gel permeation chromatography. The ¹H-NMR chart of the obtained polymer was almost the same as that of the monomer; FT-IR spectra indicated the existence of carboxyl groups. The weight-average molecular weight of the soluble part in tetrahydrofuran was found to be 1,451. Dispersion polymerization of p-hydroxycinnamic acid was carried out in a mixture solution of methanol and phosphate buffer solution by adding a dispersion stabilizer. Of the several such polymers tested, poly(vinyl alcohol) was found to be the most effective in producing reactive poly(p-hydroxycinnamic acid) microspheres.     

One-pot two-step synthesis of 4-vinylphenols from 4-hydroxy substituted benzaldehydes under microwave irradiation: a new perspective on the classical Knoevenagel-Doebner reaction

The classical Knoevenagel-Doebner reaction is reinvestigated wherein the direct synthesis of substituted 4-vinylphenols instead of the expected 4-hydroxycinnamic acids is described. The condensation reaction is performed on 4-hydroxy substituted benzaldehydes and malonic acid with a mixture of acetic acid-piperidine as condensing agent under focused microwave irradiation. The occurrence of simultaneous condensation-double decarboxylation without the use of any decarboxylating agent is a new finding, the reaction being facilitated solely by the hydroxy substituent and microwave irradiation effect.     

Obtaining 4-vinylphenols by decarboxylation of natural 4-hydroxycinnamic acids under microwave irradiation

4-Vinylphenols, useful compounds for industrial applications, were obtained by decarboxylation of 4-hydroxycinnamic acids under microwave irradiation in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base and basic aluminum oxide as solid support. The reactions were fast (15-30 min). The selective extraction of the final products with ethyl acetate avoids chromatographic purifications. The conversions are quantitative and the yields are satisfactory. Only the unstable 4-vinylcatechol was obtained in moderate yield. This procedure was successfully extended to a natural sample of ferulic acid extracted from wheat bran to get the corresponding 4-vinylguaiacol, a FEMA GRAS (Flavor and Extract Manufacturer's Association; General Regarded as Safe) approved flavoring agent.     

Asymmetric solid-phase synthesis of (3'R,4'R)-di-O-cis-acyl 3-carboxyl khellactones

[formula: see text] We describe a practical parallel synthesis of (3'R,4'R)-di-O-cis-acyl 3-carboxyl khellactones on a solid phase in high yield. The highlights of this synthesis include a Knoevenagel condensation, asymmetric dihydroxylation, catalyzed acylation, and product cleavage from the solid support.     

Synthesis of poly(ether esters) from reaction of alpha-cyano-4-hydroxycinnamic acid and group IVB metallocenes

Poly(ether esters) are rapidly synthesized in moderate yield employing the interfacial polycondensation reaction system from the reaction of alpha-cyano-4-hydroxycinnamic acid and Group IVB metallocenes. The products are high polymers. Infrared spectroscopy shows the formation of new bands derived from the M-O and M-O(CO) linkages. It also shows that the products exist as alternating M-O and M-O(CO) linkages. The products show outstanding inhibition of a variety of cancer cell lines including two pancreatic cancer cell lines. EC₅₀ values for the polymers are in the nanogram/mL range. The ability to inhibit the cancer cell lines is generally Hf>Zr>Ti. Thus, future synthesis and testing might consider using compounds containing hafnocene and zirconocene in addition to the titanocene moiety.     

Carbonylative Sonogashira annulation sequence: One-pot synthesis of 4-quinolone and 4H-chromen-4-one derivatives

Carbonylative Sonogashira annulation sequence for one pot synthesis of 4-quinolone and 4H-chromen-4-one has been developed in presence of Pd-NHC catalyst. Substituted 2-iodoaniline and 2-iodophenol independently underwent in the carbonylative Sonogashira annulation reaction with a variety of acetylenes to result in 4-quinolone and flavone derivatives respectively in good to excellent yield. Moreover, this protocol does not require toxic CO gas, high catalyst loading and any expensive salt/additive. Herein we, for the first time, are using Mo(CO)₆, as solid CO source for the one pot synthesis of flavone derivatives via carbonylative Sonogashira annulation reaction.     

Improved synthesis of the valuable peptidomimetic intermediate 3-azido-4-hydroxy cyclopentanoic acid

An improved synthesis of 3-azido-4-hydroxy cyclopentanoic acid 2 is presented. This molecule is useful as a synthetic scaffold for β-turn mimetics on solid phase, with the selectivity of the turns being dependent on the diastereomer employed. A high diastereoselectivity in the synthesis of this molecule in solution is reported, which may then be attached to the solid phase for the synthesis of peptidomimetic libraries.     

Study of matrix and polymer substrate in MALDI-TOF mass spectrometry of DNA

Protein matrices such as 3,5-dimethoxy-4-hydroxycinnamic acid (sinapinic acid, SA) and a-cyano-4-hydroxycinnamic acid (CHCA) tend to yield homogeneous dried spots. However, well known MALDI matrices for single- and double-stranded DNA such as 3-hydroxy picolinic acid (HPA) and picolinic acid (PA) forms the crystals at the rim of their spots with uneven distribution of matrix and DNA. This inhomogeneous deposition of DNA-doped matrix crystals at the MALDI spot requires a search for sweet spots. It is important to obtain homogeneous MALDI spots that yield signals not only from the periphery but the entire spot for automated, high throughput MALDI-TOF analysis of short DNA fragments. We have investigated the characteristics of MALDI matrices for DNA and presented a method for improving the homogeneity of MALDI samples by using polymer substrates such as linear polyacrylamide (LPA), poly(ethylene oxide) (PEO), methyl cellulose (MC) and Nafion.     

Improved method for synthesis of 7-amino-4-methylcoumarin

A new variant of the synthesis of 7-amino-4-methyl-coumarin from m-aminophenol via a three-step scheme is proposed. Acylation of m-aminophenyl with methoxycarbonyl chloride gave m-(N-methoxycarbonylamino)phenol, which was converted to 7-(N-methoxycarbonyl-amino)-4-methylcoumarin by condensation with acetoacetic ester in sulfuric acid. Heating of the coumarin with concentrated alkali leads to an intermediate, which, after acidification, is converted to 7-amino-4-methylcoumarin in high yield.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 312–314, March, 1990.     

Sublimation as a method of matrix application for mass spectrometric imaging

Common organic matrix-assisted laser desorption/ionization (MALDI) matrices, 2,5-dihydroxybenzoic acid, 3,5-dimethoxy-4-hydroxycinnamic acid, and alpha-cyano-4-hydroxycinnamic acid, were found to undergo sublimation without decomposition under conditions of reduced pressure and elevated temperature. This solid to vapor-phase transition was exploited to apply MALDI matrix onto tissue samples over a broad surface in a solvent-free application for mass spectrometric imaging. Sublimation of matrix produced an even layer of small crystals across the sample plate. The deposition was readily controlled with time, temperature, and pressure settings and was highly reproducible from one sample to the next. Mass spectrometric images acquired from phospholipid standards robotically spotted onto a MALDI plate yielded a more intense, even signal with fewer sodium adducts when matrix was applied by sublimation relative to samples where matrix was deposited by an electrospray technique. MALDI matrix could be readily applied to tissue sections on glass slides and stainless steel MALDI plate inserts as long as good thermal contact was made with the condenser of the sublimation device. Sections of mouse brain were coated with matrix applied by sublimation and were imaged using a Q-q-TOF mass spectrometer to yield mass spectral images of very high quality. Image quality is likely enhanced by several features of this technique including the microcrystalline morphology of the deposited matrix, increased purity of deposited matrix, and evenness of deposition. This inexpensive method was reproducible and eliminated the potential for spreading of analytes arising from solvent deposition during matrix application.     

Novel solid acid with both Brønsted and Lewis acid sites for biodiesel synthesis

The solid acid with both Brønsted and Lewis acid sites has been synthesized from resorcinol-formaldehyde (RF) resin, hydroxyethylsulfonic acid and copper hydroxyethylsulfonate. The solid acid was applied to catalyze the transesterification of rapeseed oil. The results showed that the novel solid acid was very efficient for the biodiesel synthesis with the yield over 99% even for the rapeseed oil with high water content and both the free fatty acid and triglyceride could be efficiently transformed to the biodiesel products. The regular sphere structure, low cost, high acidity and catalytic activities gave the solid acid great potential for green chemical processes.     

Solid-phase synthesis of urea and amide libraries using the T2 triazene linker

Starting from Merrifield resin, primary amines were immobilized in two steps by triazene linkage (T2-linker). While reaction with isocyanates gave rise to resin-bound urea derivatives, acylation by acid chlorides or anhydrides furnished amides bound to solid support via the nitrogen atom, therefore representing a novel backbone amide linker. Cleavage from the resin was conducted using dilute trimethylsilyl chloride or trifluoroacetic acid, respectively, to yield ureas and amines/amides in a library format (altogether 60 examples; manual synthesis: 17 ureas, 6 mono-alkylated ureas [including dihydroxylation and ozonolysis/Wittig reaction]; automated synthesis: 15 ureas, 15 amides) in high purities and good overall yields. The synthesis of a small library (4 x 4 member) was successfully conducted on a Bohdan Neptune synthesizer.     

Green synthesis of 3,4-dihydropyrimidinones using nano Fe3O4@meglumine sulfonic acid as a new efficient solid acid catalyst under microwave irradiation

Design, synthesis and characterization of nano Fe₃O₄@meglumine sulfonic acid as a new solid acid catalyst for the simple and green one pot multicomponent synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones was studied. New solid acid catalyst was prepared through a clean and simple protocol and characterized using FTIR, VSM, TGA, SEM, elemental analysis (CHN) and XRD techniques. Heterogenization of homogeneous catalyst as a green approach is a useful method for enhancing the efficiency of catalyst. Presented study was a new method for attachment of homogeneous highly soluble catalyst (meglumine sulfate) to the magnetite nanoparticle surfaces for preparing a heterogeneous and effective catalyst. Obtained heterogeneous and reusable solid acid catalyst has high performance in the synthesis of Biginelli compounds. The reaction was performed under microwave irradiation as a rapid and green condition. Easy work up as well as excellent yield (90–98%) of products in short reaction times (40–200 s) and reusable catalyst are the main advantages of presented procedure. Reaction products were characterized in details using physical and chemical techniques such as melting point, ¹H NMR, ¹³C NMR and FTIR.     

A convenient and scalable synthesis of ethyl N-[(2-Boc-amino)ethyl]glycinate and its hydrochloride. Key intermediates for peptide nucleic acid synthesis

An improved synthesis of ethyl N-[(2-Boc-amino)ethyl]glycinate and its hydrochloride salt is reported. The synthesis is based on the reductive alkylation of Boc-ethylenediamine with ethyl glyoxylate hydrate and furnishes the title compound in near quantitative yield and high purity without chromatography. This compound is suitable, as is, for the synthesis peptide nucleic acid monomers. Further, conversion to the hydrochloride salt provides a stable, nonhygroscopic solid that is a convenient form for handling and storage.     

Mechanistic investigation and implications of a sacrificial aniline for the tandem cascade synthesis of 4-aza-podophyllotoxin analogues

Mechanistic investigations were pursued to determine a plausible mechanism in the cascade reaction involving tetronic acid with aldehydes and anilines to generate the 4-aza-2,3-dehydropodophyllotoxin core structure. The mechanistic driven hypothesis paved the way for a new reaction design using for the first time a sacrificial electron deficient aniline leading to an optimized cascade protocol (up to threefold yield improvement) for the synthesis of novel 4-aza-2,3-dehydropodophyllotoxin analogues.     

A practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid,an antirheumatic agent (part 1)

An efficient and practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (1), a new antirheumatic drug, has been developed. The intermediate, 2-methylene-4-(4-methylphenyl)-4-oxobutanoic acid (2), was prepared by Friedel-Crafts acylation of toluene with itaconic anhydride (3) in the presence of aluminum trichloride and nitrobenzene in 63% yield without silica gel column purification. Compound 1 was prepared by Michael addition of 2 with thioacetic acid (4) in 74% yield. Overall, 1 was obtained in 47% yield from 3. The structures and synthetic mechanisms of by-products (five compounds) of 2 were also clarified.     

高效可回收聚(4-乙烯基吡啶)高氯酸催化剂用于合成双香豆素和双吲哚(英文)

Poly(4-vinylpyridinium) perchlorate has been used as an efficient solid acid catalyst for the synthesis of 3,3'-(arylmethylene)bis(4-hydroxycoumarins) and bis(indolyl)methanes, with the products being formed in excellent yields over very short reaction times under mild and environmentally friendly conditions. This catalyst can be reused several times without any appreciable loss in its activity.     

A short enantioselective synthesis of homocitric acid-γ-lactone and 4-hydroxy-homocitric acid-γ-lactones

A simple method for the synthesis of enantiopure homocitric acid γ-lactone and its 4-hydroxy analogues starting from spiro-γ-dilactone, in up to 74% isolated yield is described.     

A new pathway via intermediate 4-amino-3-fluorophenol for the synthesis of regorafenib

A practical synthetic route to regorafenib, in which the target compound was obtained via a 10-step synthesis starting from 2-picolinic acid, 4-chloro-3-(trifluoromethyl)aniline, and 3-fluorophenol, is reported. Crucial to the strategy is the preparation of 4-amino-3-fluorophenol via Fries and Beckman rearrangements using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and an acceptable overall yield. A scale-up experiment was carried out to provide regorafenib with 99.96% purity in 46.5% total yield.     

稀土固体超强酸SO~4^2^-/TiO~2/La^3^+催化合成水杨酸 异丁酯

研究了以稀土固体超强酸SO~4^2^-/TiO~2/La^3^+为催化剂,水杨酸和异丁醇为原料合成水杨酸异丁酯,并考察了影响反应的因素。结果表明,醇酸比为3:1,催化剂用量为1.0g(水杨酸为0.1mol的情况下),带水剂苯为15mL,反应时间为3.0h是最适宜的反应条件,酯化率达96.2%。