4,6-Dimethoxy-1,3,5-triazine oligoxyloglucans: Novel one-step preparable substrates for studying action of endo-β-1,4-glucanase III from Trichoderma reesei

Two kinds of 4,6-dimethoxy-1,3,5-triazine (DMT) oligoxyloglucans, DMT-β-XXXG and DMT-β-XLLG, have been synthesized via one-step procedure starting from the corresponding unprotected oligoxyloglucans in water. The resulting DMT derivatives were found to be hydrolyzed by endo-β-1,4-d-glucanase III from Trichoderma reesei (EGIII) and utilized as substrates for determination of the kinetic parameters of EGIII. The present DMT-method would be a convenient analytical tool for studying the action of glycosyl hydrolases due to the extremely simple synthetic process of DMT-glycosides without using protecting groups.     

The expedient synthesis of 1,5-benzothiazepines as a family of cytotoxic drugs

The expedient synthesis of 1,5-benzothiazepines using LaY zeolite under stirring condition is reported and synthesized compound screened for cytotoxic activity. The reaction produces the product in relatively low yields and requires a long time when they were performed in various solvents under conventional and microwave irradiation. Thus, the procedure provides a simple and green synthetic methodology under environmentally friendly conditions.     

A Review of: “Polymers: Their Properties and Blood Compatibility S. Dawids,Ed. Kluwer,Dordrecht; Boston; London, 1989; hardbound, 410 pages, $120.00”

[BPy]H₂PO₄ was easily prepared and used as an efficient and recyclable catalyst for the one-pot synthesis of 2,4,5-trisubstituted imidazoles under solvent-free conditions in good to excellent yields. Solvent-free conditions, simple experimental and workup procedures, and the use of a nontoxic, recyclable catalyst of an environmentally benign nature are remarkable features of the procedure.     

Initial-phase optimization for bioremediation of munition compound-contaminated soils.

We examined the bioremediation of soils contaminated with the munition compounds 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine, and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetraazocine by a procedure that produced anaerobic conditions in the soils and promoted the biodegradation of nitroaromatic contaminants. This procedure consisted of flooding the soils with 50 mM phosphate buffer, adding starch as a supplemental carbon substrate, and incubating under static conditions. Aerobic heterotrophs, present naturally in the soil or added as an inoculum, quickly removed the oxygen from the static cultures, creating anaerobic conditions. Removal of parent TNT molecules from the soil cultures by the strictly anaerobic microflora occurred within 4 days. The reduced intermediates formed from TNT and hexahydro-1,3,5-trinitro-1,3,5-triazine were removed from the cultures within 24 days, completing the first stage of remediation. The procedure was effective over a range of incubation temperatures, 20 to 37 degrees C, and was improved when 25 mM ammonium was added to cultures buffered with 50 mM potassium phosphate. Ammonium phosphate buffer (50 mM), however, completely inhibited TNT reduction. The optimal pH for the first stage of remediation was between 6.5 and 7.0. When soils were incubated under aerobic conditions or under anaerobic conditions at alkaline pHs, the TNT biodegradation intermediates polymerized. Polymerization was not observed at neutral to slightly acidic pHs under anaerobic conditions. Completion of the first stage of remediation of munition compound-contaminated soils resulted in aqueous supernatants that contained no munition residues or aminoaromatic compounds.     

Claisen–Schmidt condensation: Synthesis of (1S,6R)/(1R,6S)‐2‐oxo‐N,4,6‐triarylcyclohex‐3‐enecarboxamide derivatives with different substituents in H2O/EtOH

A simple, green, and direct three‐component condensation of acetophenone, aromatic aldehydes with 3‐oxo‐N‐phenylbutanamide (acetoacetanilide) to generate some novel (1S,6R)/(1R,6S)‐2‐oxo‐N,4,6‐triarylcyclohex‐3‐enecarboxamide derivatives was carried out over K₂CO₃ (10 mol%) with high efficiency in water/ethanol as green solvent at room temperature. This protocol proceeded via Claisen–Schmidt condensation and Michael addition. The present methodology offers several advantages, such as short reaction time, high yield, more readily available and inexpensive materials, more environmentally friendly, no need for column chromatography, simple work‐up procedure, and the absence of volatile and hazardous organic solvents.     

Synthesis of glycosides in which the aglycon is an N-(Hydroxymethyl)amino-1,3,5-triazine derivative

The synthesis of analogues of the anti-tumour drug 2-[N-(hydroxymethyl)methylamino]-4,6-bis (dimethylamino)-1,3,5-triazine (HMPMM) in which the OH or a dimethylamino group is replaced by a carbohydrate has been explored. Triazinyl β-glycosides were readily prepared by reaction of sugars with trimethyl-triazinylammonium salts. These were made with one or two methylamino groups on the triazine for reaction with formaldehyde to give the cytotoxic NMeCH2OH group. However, reaction of the triazinyl glycosides with formaldehyde gave complex intractable mixtures. When the carbohydrate portion was changed to the fully protected 2,3,4,6-tetra-O-acetyl glucose a good yield of the 2-[N-(hydroxymethyl)methylamino]-4-(dimethylamino)-1,3,5-triazin-2-yl tetra-O-acetyl β-glucoside was obtained. However, de-acetylation using sodium methoxide also removed the N–CH2OH group. We are investigating protection of the base-sensitive N–CH2OH group as trialkylsilyl and benzyl ethers and are looking at de-acetylation methods that are more selective. We have prepared glycosides in which the sugar is joined through the oxygen of the NMeCH2OH group. Coupling of acetobromoglucose with HMPMM catalysed by silver salts was not successful. Although methyl and cyclohexyl derivatives of HMPMM may be produced in high yields by reaction of HMPMM with methyl and cyclohexyl alcohols under acidic catalysis, production of glycosides in this way gave poor yields. MNDO calculations on reactions of HMPMM helped us devise improved reaction conditions for the condensation of 2,3,4,6-tetra-O-acetyl glucose with HMPMM and its derivatives. The best procedure to generate one of the target glycosides is to react 2,3,4,6-tetra-O-acetyl glucose and formaldehyde with 2-methylamino- 4,6-bis(dimethylamino)-1,3,5-triazine. The β-glycoside product was de-acetylated using potassium carbonate in dry methanol. Abbreviations: HMM, hexamethylmelamine (2) or 2,4,6-tris(dimethylamino)-1,3,5-triazine; HMPMM, hydroxymethylpentamethylmelamine or 2-[N-(hydroxymethyl)-methylamino]-4,6-bis(dimethylamino)-1,3,5-triazine; PMM, Pentamethylmelamine or 2-methylamino-4,6-bis(dimethylamino)-1,3,5-triazine; TBMS, t-Butyldimethylsilyl; p-TSA, p-Toluenesulphonic acid This revised version was published online in November 2006 with corrections to the Cover Date.     

Aqua mediated synthesis of substituted 2-amino-4H-chromenes and in vitro study as antibacterial agents

A simple, clean, environmentally benign route to the synthesis of 2-amino-chromenes is described using K2CO3 as a green catalyst in water under microwave irradiation. This implies a convenient route avoiding the usage of hazardous organic solvents and organic bases. This technique requires only water in both the reaction step and workup, thus rendering the whole procedure into a truly ecofriendly green protocol. All the synthesized compounds were shown to possess antibacterial activity as tested in vitro against standard strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.     

Synthesis and antinociceptive-antimicrobial activities of some new amide derivatives of 3,5-di/-and 1,3,5-trimethylpyrazoles

Some N-(3,5-di-/1,3,5-trimethylpyrazole-4-yl)-4-substitutedbenzamide derivatives were prepared as possible antiociceptive-antimicrobial agents. New amide derivatives (3-12) were synthesized by reacting 4-amino-3,5-di and 1,3,5-trimethylpyrazoles with 4-substitutedbenzoyl chlorides. Hotplate and tail-immersion tests were used for the determination of the antinociceptive activity. Morphine, was used as a standard test drug. All compounds were administered at a dose of 100 mg/kg ip and some of them had significant antinociceptive activity in both tests. Compound 10 (N-(1,3,5-trimethylpyrazole-4-yl)-4-bromobenzamide), was the most active one in both tests among the compounds. The antinociceptive activity of the compounds 10, 11 (N-(1,3,5-trimethylpyrazole-4-yl)-4-chlorobenzamide), and 12 (N-(1,3,5-trimethylpyrazole-4-yl)-4-fluorobenzamide), started at 30 minutes and continued up to 150 minutes in the hotplate test. Also compounds were tested for their in vitro antimicrobial activity, but exhibited weak antibacterial activity.     

Novel 13β- and 13α-d-homo steroids: 17a-carboxamido-d-homoestra-1,3,5(10),17-tetraene derivatives via palladium-catalyzed aminocarbonylations

17a-Methoxycarbonyl- and 17a-carboxamido-d-homoestra-1,3,5(10),17-tetraene derivatives were synthesized by palladium-catalyzed carbonylation reactions of the corresponding 17a-iodo-d-homoestra-1,3,5(10),17-tetraene derivatives using methanol and various amines as O- and N-nucleophiles, respectively. Both the natural (13β) and the epi (13α) series of compounds were isolated. The 17a-iodo-17-ene functionalities in the two 13-epimer series differ in reactivity. While the aminocarbonylations were practically complete in the 13β series in reasonable reaction time under mild conditions and high isolated yields were achieved, the corresponding 13α-17a-iodo-17-ene substrate has shown decreased reactivity resulting in moderate to low yields. However, under high carbon monoxide pressure (40 bar) excellent yields can be obtained even in the 13α series. The aminocarbonylation was completely chemoselective in both series, i.e., the corresponding 17a-carboxamido-17-ene derivatives were formed exclusively.     

Photosynthetic electron transport inhibition by 2-substituted 4-alkyl-6-benzylamino-1,3,5-triazines with thylakoids from wild-type and atrazine-resistant Chenopodium album

The effect of 2-benzylamino-1,3,5-triazines on photosynthetic electron transport (PET) was measured with thylakoids isolated from atrazine-resistant, wild-type Chenopodium album, and spinach to find novel 1,3,5-triazine herbicides bearing a strong PET inhibition. The PET inhibition assay with Chenopodium (wild-type and resistant), yielded a resistance ratio (R/W = I50 (resistant)/I50 (wild-type)) of 324 for atrazine while for benzylamino-1,3,5-triazine derivatives of diamino-1,3,5-triazines a R/W of 11 to 160 was found. The compounds having a benzylamino group at one of the amino groups in the diamino-1,3,5-triazines have a resistant ratio down to one half to 1/30 of the atrazine value. The average resistance ratio of 21 benzylamino derivatives of monoamino-1,3,5-triazines was found to be about 4.0. The inhibition of 21 benzylamino-1,3,5-triazines assayed with atrazine-resistant Chenopodium thylakoids, indicated by pI50 (R)-values, correlated well with the PET inhibition pI50 (W) of wild-type thylakoids from Chenopodium.     

1,2-Dimethylimidazole-4-sulfonyl chloride, a novel derivatization reagent for the analysis of phenolic compounds by liquid chromatography electrospray tandem mass spectrometry: application to 1-hydroxypyrene in human urine

A novel derivatization method employing 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC) to improve the mass spectrometric response for phenolic compounds in liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) and tandem mass spectrometry (LC-ESI-MS/MS) is described. Several environmentally relevant compounds, including chloro-, aryl- and alkylphenols, steroidal estrogens, and hydroxy-polycyclic aromatic hydrocarbons (OHPAHs), were selected to evaluate this technique. A facile derivatization procedure employing DMISC results in dimethylimidazolesulfonyl (DMIS) derivatives that are stable in aqueous solution. These DMIS derivatives produced intense [M+H](+) ions in positive-ion LC-ESI-MS. The product ion spectra of the [M+H](+) ions of simple phenols were dominated by ions representing the DMIS and dimethylimidazole moieties, whereas product ion spectra of the DMIS derivatives of OHPAHs with three or more fused aromatic rings showed prominent ArO(+) ions, the relative intensity of which increased with the number of rings. The DMIS derivatives of the selected phenolic compounds showed excellent chromatographic properties. To substantiate the utility of derivatization with DMISC, an analytical method employing enzyme hydrolysis, solid phase extraction, derivatization with DMISC, and analysis by LC-ESI-MS/MS with multiple reaction monitoring for determination in human urine of 1-hydroxypyrene, a widely used biomarker for the assessment of human exposure to PAHs, was developed and validated.     

Rapid and sensitive procedure for the separation and quantitation of - and -serine in rat brain using gas chromatography-mass spectrometry

A very simple and rapid GC-MS procedure for the separation and quantitation of - and -serine has been developed utilizing a conventional bonded-phase capillary column. The procedure involves initial esterification with isobutanol followed by acylation with the chiral derivatizing reagent S-(−)-N-(heptafluorobutyryl)prolyl chloride (HPC). This procedure requires neither extraction nor clean-up steps and is sensitive to 50 pg on-column. Total time of the procedure is under 3 h and derivatives are stable at room temperature for at least 5 days, making this procedure ideal for automated injections. A simple, one-day synthesis of HPC is described which yields >99.9% optical purity.     

An innovative method for oxidative degradation of chitosan with molecular oxygen catalyzed by metal phthalocyanine in neutral ionic liquid

A novel aqueous solution-ionic liquid biphasic catalytic system was established for the oxidative degradation of chitosan under mild conditions. In this process, the environmentally acceptable and inexpensive molecular oxygen was first used as oxidant, the metal phthalocyanine was immobilized in ionic liquid as catalyst, and the aqueous solution as medium carried the reactants and the products. Under vigorous stirring and heating, the reactants fully contacted the catalysts in the emulsion and chitosan efficiently degraded into water-soluble materials. At the end of the reaction, the catalytic system could be easily separated by simple decantation and could also be reused in subsequent runs without apparent change in activity. These characters are in favor of the elimination of pollution and the reduction of the economic cost in the large-scale production of the water-soluble chitosan derivatives in chemical industry.     

Preparation of 1,3,5-thiadiazine-2-thione derivatives of chitosan and their potential antioxidant activity in vitro

Three new kinds of 1,3,5-thiadiazine-2-thione derivatives of chitosan with two different molecular weight (SATTCS1, SATTCS2, TITTCS1, TITTCS2, CITTCS1 and CITTCS2) have been prepared. Their structures were characterized by IR spectroscopy. The substitution degree of derivatives calculated by elemental analyses was 0.47, 0.42, 0.41, 0.38, 0.41 and 0.36, respectively. The result shows that substitution degree of derivatives was higher with lower molecular weight. The antioxidant activity was studied using an established system, such as hydroxyl radical scavenging, superoxide radical scavenging and reducing power. Antioxidant activity of the 1,3,5-thiadiazine-2-thione derivatives of chitosan were stronger than that of chitosans and antioxidant activity of low molecular weight derivatives were stronger than that of high molecular weight derivatives. It is a potential antioxidant in vitro.     

Synthesis and antinociceptive-antimicrobial activities of some new amide derivatives of 3,5-di/-and 1,3,5-trimethylpyrazoles

Some N-(3,5-di-/1,3,5-trimethylpyrazole-4-yl)-4-substitutedbenzamide derivatives were prepared as possible antiociceptive-antimicrobial agents. New amide derivatives (3–12) were synthesized by reacting 4-amino-3,5-di and 1,3,5-trimethylpyrazoles with 4-substitutedbenzoyl chlorides. Hotplate and tail-immersion tests were used for the determination of the antinociceptive activity. Morphine, was used as a standard test drug. All compounds were administered at a dose of 100 mg/kg ip and some of them had significant antinociceptive activity in both tests. Compound 10 (N-(1,3,5-trimethylpyrazole-4-yl)-4-bromobenzamide), was the most active one in both tests among the compounds. The antinociceptive activity of the compounds 10, 11 (N-(1,3,5-trimethylpyrazole-4-yl)-4-chlorobenzamide), and 12 (N-(1,3,5-trimethylpyrazole-4-yl)-4-fluorobenzamide), started at 30 minutes and continued up to 150 minutes in the hotplate test. Also compounds were tested for their in vitro antimicrobial activity, but exhibited weak antibacterial activity.     

Enhancing the Potential for in situ Bioremediation of RDX Contaminated Soil from a Former Military Demolition Range

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a toxic, mobile groundwater contaminant common to military sites. Biodegradation of RDX is an alternative, cost effective and environmentally friendly remediation approach. The effects of carbon amendments (waste glycerol and cheese whey) used alone or with a potential electron shuttle (ammonium lignosulfonate) on RDX biodegradation were assessed. These substrates are readily available waste materials that can be used as nutrients to promote oxygen consumption, creating a more reducing environment. Nutrient amended batch assays were conducted using RDX spiked contaminated demolition range soil under anaerobic conditions. The amendments that improved RDX mineralization the most were subsequently tested in a scaled up repacked soil column study to verify if this strategy could be effectively implemented on-site. Microcosm results indicated that RDX mineralization by indigenous anaerobic microorganisms was enhanced the most by the low carbon amendment concentration. The use of ammonium lignosulfonate was not effective, exhibiting an inhibitory effect on RDX biodegradation that was stronger at higher concentrations. The soil column study showed that the low concentration of waste was the most promising treatment scenario. These results offer good prospects for the use of waste glycerol for in situ treatment of soils contaminated with energetic-materials, such as RDX.     

Application of PEG-400 as a green biodegradable polymeric medium for the catalyst-free synthesis of spiro-dihydropyridines and their use as acetyl and butyrylcholinesterase inhibitors

A simple, efficient and green approach for the synthesis of spiro-dihydropyridines derivatives by one-pot multi-component reaction of isatin or acenaphthoquinone derivatives (1 equiv) with malononitrile (1 equiv) and N,N′-substituted-2-nitroethene-1,1-diamines (1 equiv) in PEG-400 under catalyst-free conditions is described. This method provides several advantages such as environmental friendliness, short reaction time, and simple workup procedure for the synthesis of biologically important compounds. The ability of synthesized compounds in inhibition of acetyl and butyrylcholinesterase were investigated both in vitro and in silico. All compounds showed moderate to high level activity against both acetyl and butyrylcholinesterase. There was a good correlation between in vitro and in silico studies.     

Examination of the mutagenicity of RDX and its N-nitroso metabolites using the Salmonella reverse mutation assay

The mutagenicity of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and its N-nitroso derivatives hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) were evaluated using the Salmonella tryphimurium reverse mutation assay (Ames assay) with strains TA97a, TA98, TA100, and TA102. Using a preincubation procedure and high S9 activation (9%), RDX was observed to induce weak mutagenesis to strain TA97a with a mutagenicity index (MI) of 1.5-2.0 at a dose range of 32.7-1090microg/plate. MNX induced moderate mutagenesis to strain TA97a with an MI of 1.6-2.8 at a dose range of 21.7-878microg/plate. TNX also induced moderate mutagenesis in strain TA97a with an MI of 2.0-3.5 to TA97a at a dose range of 22.7-1120microg/plate. TNX also caused weak mutagenesis to strain TA100 with S9 activation at the dose of 1200microg/plate. MNX and TNX induced weak to moderate mutagenesis to strain TA102. Strain TA97a was found to be the most sensitive strain among these four strains. No cytotoxicity of RDX, MNX, and TNX was observed at the concentrations used in this study. Doses were verified by HPLC.     

γ-Lactam-Based Antifungal Compounds against the Wheat Pathogen Zymoseptoria tritici

As new environmentally friendly and effective antifungal agents are deeply needed, efficient ecofriendly strategies were designed to access two series of compounds inspired from natural γ-lactams. Designed compounds were fully characterized and evaluated as antifungal candidates against Zymoseptoria tritici, the main pathogen on wheat crops. The targeted derivatives were prepared from natural resources using green solvents, simple procedures, and limited purification steps. These bio-inspired compounds revealed as good candidates for further development of efficient crop protection products. Indeed, the HIT compounds exhibited IC₅₀ around 1 μg/mL and were more active than the references tebuconazole and bixafen towards some multidrug-resistant strains. Two dozen of derivatives have been obtained for each series and allowed to establish early structure-activity relationships useful for the development of next generation of γ-lactam derivatives with improved efficacy.     

A modified system for thiazolinone conversion to thiohydantoin derivatives and their separation by high-pressure liquid chromatography

An improved and very simple procedure for thiazolinone conversion to thiohydantoin derivatives and their separation by reverse-phase high-pressure liquid chromatography is described. Trifluoroacetic acid (10%) in ethyl acetate has been employed as a conversion reagent to circumvent the deamidation of acid amides and methylation of acidic amino acids, with a concomitant increase in the detection limits of these residues. Additionally, a very simple procedure has been developed for the separation of phenylthiohydantoin (PTH) derivatives of amino acids. The system takes advantage of the computer-controlled precise mixing of the solvents A and B to achieve accurate pH and thus avoid the necessity of pH adjustment of a buffer. The procedure is simple and highly reproducible, and separates all the 20 known PTH amino acids. The efficiency of the method has been examined on synthetic and natural proteins/peptides, in manual and autoconversion systems, over a period of more than 18 months.