Synthesis of chiral 3,4,5,6-tetrahydro-1,4-thiazin-2-ones (thiamorpholin-2-ones)-novel heterocycles possessing enhanced carbonyl electrophilicity over their oxygen counterparts

We report herein the first synthesis of chiral derivatives possessing the 1,4-thiazinone core. As predicted, the thiolactone is more susceptible to nucleophilic attack than the equivalent lactone system.

Solvent extraction of Am(III) and Eu(III) from nitrate solution using synergistic mixtures of n-tridentate heterocycles and chlorinated cobalt dicarbollide

The separation by solvent extraction of Am-241(III) from Eu-152(III), in 1 M NaNO3 weakly acidic (pH 4) aqueous solutions, into dilute (ca. 10(-2) M) solutions of triazinylbipyridine derivatives (diethylhemi-BTP or di(benzyloxyphenyl) hemi-BTP) and chlorinated cobalt dicarbollide (COSAN) in 1-octanol or nitrobenzene has been studied. The N-tridentate heterocyclic ligands, which are selective for Am(III) over Eu(III), secured efficient separation of the two metal ions, while COSAN, strongly hydrophobic and fully dissociated in polar diluents, enhanced the extraction of the metal ions by ion-pair formation. Molecular interactions between the two co-extractants, observed at higher concentrations, led to the precipitation of their 1: 1 molecular adduct. In spite of that, efficient separations of Am and Eu ions were attained, with high separation factors, SFAm/Eu of 40 and even 60, provided the concentration of hemi-BTP was significantly greater than that of COSAN. Excess COSAN concentrations caused an antagonistic effect, decreasing both the distribution ratio of the metal ions and their separation factor.

Synthesis of linked heterocycles via use of bis-acetylenic compounds

Linked bis-pyrazoles, a pyrazolyl-isoxazole, a pyrazolyl-pyrimidine and a pyrazolyl-triazole were synthesized starting with commercially available 1,4-bis(trimethylsilyl)-1,3-butadiyne 1 or readily available bis-acetylenic diketone 22. A stepwise approach based on the use of 1 allowed the synthesis of nonsymmetrically substituted bis-pyrazoles and linked heterocycles with two different cores whereas a symmetric approach based on the use of 22 allowed a very short synthesis of symmetric bis-pyrazoles.

Unravelling the conundrum of tannins in animal nutrition and health

This paper examines the nutritional and veterinary effects of tannins on ruminants and makes some comparisons with non-ruminants. Tannin chemistry per se is not covered and readers are referred to several excellent reviews instead: (a) Okuda T et al. Heterocycles 30:1195-1218 (1990); (b) Ferreira D and Slade D. Nat Prod Rep 19:517-541 (2002); (c) Yoshida T et al. In Studies in Natural Product Chemistry. Elsevier Science, Amsterdam, pp. 395-453 (2000); (d) Khanbabaee K and van Ree T. Nat Prod Rep 18:641-649 (2001); (e) Okuda et al. Phytochemistvy 55:513-529 (2000). The effects of tannins on rumen micro-organisms are also not reviewed, as these have been addressed by others: (a) McSweeney CS et al. Anim Feed Sci Technol 91:83-93 (2001); (b) Smith AH and Mackie RI. Appl Environ Microbiol 70:1104-1115 (2004). This paper deals first with the nutritional effects of tannins in animal feeds, their qualitative and quantitative diversity, and the implications of tannin-protein complexation. It then summarises the known physiological and harmful effects and discusses the equivocal evidence of the bioavailability of tannins. Issues concerning tannin metabolism and systemic effects are also considered. Opportunities are presented on how to treat feeds with high tannin contents, and some lesser-known but successful feeding strategies are highlighted. Recent research has explored the use of tannins for preventing animal deaths from bloat, for reducing intestinal parasites and for lowering gaseous ammonia and methane emissions. Finally, several tannin assays and a hypothesis are discussed that merit further investigation in order to assess their suitability for predicting animal responses. The aim is to provoke discussion and spur readers into new approaches. An attempt is made to synthesise the emerging information for relating tannin structures with their activities. Although many plants with high levels of tannins produce negative effects and require treatments, others are very useful animal feeds. Our ability to predict whether tannin-containing feeds confer positive or negative effects will depend on interdisciplinary research between animal nutritionists and plant chemists. The elucidation of tannin structure-activity relationships presents exciting opportunities for future feeding strategies that will benefit ruminants and the environment within the contexts of extensive, semi-intensive and some intensive agricultural systems. (c) 2006 Society of Chemical Industry

Unravelling the conundrum of tannins in animal nutrition and health

This paper examines the nutritional and veterinary effects of tannins on ruminants and makes some comparisons with non-ruminants. Tannin chemistry per se is not covered and readers are referred to several excellent reviews instead: (a) Okuda T et al. Heterocycles 30:1195-1218 (1990); (b) Ferreira D and Slade D. Nat Prod Rep 19:517-541 (2002); (c) Yoshida T et al. In Studies in Natural Product Chemistry. Elsevier Science, Amsterdam, pp. 395-453 (2000); (d) Khanbabaee K and van Ree T. Nat Prod Rep 18:641-649 (2001); (e) Okuda et al. Phytochemistvy 55:513-529 (2000). The effects of tannins on rumen micro-organisms are also not reviewed, as these have been addressed by others: (a) McSweeney CS et al. Anim Feed Sci Technol 91:83-93 (2001); (b) Smith AH and Mackie RI. Appl Environ Microbiol 70:1104-1115 (2004). This paper deals first with the nutritional effects of tannins in animal feeds, their qualitative and quantitative diversity, and the implications of tannin-protein complexation. It then summarises the known physiological and harmful effects and discusses the equivocal evidence of the bioavailability of tannins. Issues concerning tannin metabolism and systemic effects are also considered. Opportunities are presented on how to treat feeds with high tannin contents, and some lesser-known but successful feeding strategies are highlighted. Recent research has explored the use of tannins for preventing animal deaths from bloat, for reducing intestinal parasites and for lowering gaseous ammonia and methane emissions. Finally, several tannin assays and a hypothesis are discussed that merit further investigation in order to assess their suitability for predicting animal responses. The aim is to provoke discussion and spur readers into new approaches. An attempt is made to synthesise the emerging information for relating tannin structures with their activities. Although many plants with high levels of tannins produce negative effects and require treatments, others are very useful animal feeds. Our ability to predict whether tannin-containing feeds confer positive or negative effects will depend on interdisciplinary research between animal nutritionists and plant chemists. The elucidation of tannin structure-activity relationships presents exciting opportunities for future feeding strategies that will benefit ruminants and the environment within the contexts of extensive, semi-intensive and some intensive agricultural systems. (c) 2006 Society of Chemical Industry

QSAR studies of multidentate nitrogen ligands used in lanthanide and actinide extraction processes

Quantitative structure activity relationships (QSARs) have been developed to optimise the choice of nitrogen heterocyclic molecules that can be used to separate the minor actinides such as americium(III) from europium(III) in the aqueous PUREX raffinate of nuclear waste. Experimental data on distribution coefficients and separation factors (SFs) for 47 such ligands have been obtained and show SF values ranging from 0.61 to 100. The ligands were divided into a training set of 36 molecules to develop the QSAR and a test set of 11 molecules to validate the QSAR. Over 1500 molecular descriptors were calculated for each heterocycle and the Genetic Algorithm was used to select the most appropriate for use in multiple regression equations. Equations were developed fitting the separation factors to 6-8 molecular descriptors which gave r(2) values of >0.8 for the training set and values of >0.7 for the test set, thus showing good predictive quality. The descriptors used in the equations were primarily electronic and steric. These equations can be used to predict the separation factors of nitrogen heterocycles not yet synthesised and/or tested and hence obtain the most efficient ligands for lanthanide and actinide separation. (C) 2003 Elsevier B.V. All rights reserved.

Studies on the parallel synthesis and evaluation of new heterocyclic extractants for the partitioning of minor actinides

Multiple parallel synthesis and evaluation have been combined in order to identify new nitrogen heterocycles for the partitioning of minor actinides(III) such as americium(III) from lanthanides such as europium(Ill). An array of triazine-containing molecules was made using multiple parallel syntheses from diketones and amide hydrazides. An excess of each of the resulting purified reagents was dissolved in 1,1,2,2-tetrachloroethane containing 2-bromodecanoic acid, and equilibrated with an aqueous solution containing the radiotracers Eu-152 and Am-241 in nitric acid ([Eu] + [Am] < 400 nanomol dm(-3)). Gamma counting of the organic and aqueous phases led to the identification of several new reagents for the selective extraction of americium(III). In particular, 6-(2-pyridyl)-2-(5,6-dialkyl-1,2,4-triazaphenyl)pyridines were found to be effective reagents for the separation of americium(III) from europium(III), (SFAm/Eu was ca. 30 in [HNO3] = 0.013 mol/L).

Introduction of vinyl and hydroxymethyl functionalities at C-4 of glucose-derived substrates: synthesis of spirocyclic, bicyclic, and tricyclic nucleosides

Installing hydroxymethyl and hydroxyethyl substitutions at C-4 through vinylation and hydroboration-oxidation reactions of the C-4 bis-hydroxymethyl derivative of D-glucose based substrate, and inserting heteroatoms thereafter permitted formation of N-, O-, or S-heterocycles leading to [4,5]or [5,5]-spirocycles and a bicyclo[3.3.0]octane product. Some of the spirocycles were converted to spironucleosides under Vorbruggen glycosidation reaction conditions. Similarly, the bicyclic product was elaborated to the corresponding bicyclic nucleoside as well as an unexpected tricyclic nucleoside.

Influence of sulfur amino acids on the volatile and nonvolatile components of cooked salmon (Salmo salar)

Volatile and nonvolatile compounds, which could contribute to flavor, were analyzed in salmon. One hundred twenty-three volatile compounds were identified in the headspace of two different samples of cooked salmon, including lipid-derived volatiles, Maillard-derived volatiles, sulfur volatiles, Strecker aldehydes, nitrogen heterocyclic compounds, terpenes, and trimethylamine. Significant differences between samples were found for 104 of the volatiles. Although the levels of free cysteine and methionine were low in the salmon, sulfur volatiles were formed in the cooked fish, demonstrating that there were sufficient sulfur amino acids present for their formation. Notable differences in sulfur compounds between the samples suggested that small changes in sulfur amino acids could be responsible. When this hypothesis was tested, salmon heated with cysteine had increased levels of many thiophenes, thiazoles, alicyclic sulfides, and nitrogen heterocycles. With the addition of methionine, levels of dimethyl sulfides, two alicyclic sulfides, pyrazines, some unsaturated aldehydes, and alcohols and 2-furanmethanethiol increased. The largest difference found among the nonvolatile (low molecular weight water-soluble) compounds was in inosine monophosphate.

Synthesis and cytotoxicity studies of new dimethylamino-functionalised and hetero aryl-substituted titanocene anti-cancer drugs

From the carbolithiation of N,N-dimethylamino fulvene (3a) and different ortho-lithiated heterocycles (furan, thiophene and N-methylpyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 240, and 28 mu M for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene 5c with an IC50 value of 5.5 mu M is found to be almost as cytotoxic as cis-platin, which showed an IC50 value of 3.3 mu M, when tested on the LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself. (c) 2007 Elsevier B.V. All rights reserved.

Tuning the solubilities of bis-triazinylphenanthroline ligands (BTPhens) and their complexes

A series of bis-triazinylphenanthroline ligands (BTPhens) was synthesized by modifying the triazine substituents. It was found that varying these substituents altered the solubilities of the ligands in a number of non-polar solvents. Thus C5-BTPhen showed significantly higher solubility in octanol than C1-BTPhen. The high solubility of C5-BTPhen and its complexes was exploited to facilitate the NMR titration experiments. These experiments shown that the dominant species in solution were the 1:2 complexes [Ln(III)(BTPhen)2], even at high Ln concentrations, and that the relative stability of the 2:1 to 1:1 BTPhen-Ln complexes varied with different lanthanides. C5-BTPhen therefore shows considerable promise for a once-through selective actinide separation process.

Immobilisation of phenanthroline-bis triazine(c1-btphen) on magnetic nanoparticles for co-extraction of americium(III) and europium(III)

The present work reports a convenient route for the immobilisation of a phenanthroline-bis triazine (C1-BTPhen) group on the surface of zirconia-coated maghemite (γ-Fe2O3) magnetic nanoparticles. The magnetic nanoparticles functionalized with C1-BTPhen were able to co-extract Am(III) and Eu(III) from nitric acid (HNO3). The extraction efficiency of these C1-BTPhen-functionalized magnetic nanoparticles for both Am(III) and Eu(III) was 20% at 4M HNO3. The interaction between C1-BTPhen and metal cations is reversible. These functionalized magnetic nanoparticles can be used for the co-extraction of traces of Am(III) and Eu(III).