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Serum Antioxidant/Oxidant Balance (AOB), calculated as Antioxidant Capacity (AC)/Peroxide Level (PxL) ratio, was applied for the first time to two long-term small pilot studies: a three-week and eight-week investigations, regarding the intake of 250 g/day cherry puree and a diet including several food antioxidants, respectively. Serum AC was assayed by the new LOX-FL and the widely used ORAC and TEAC methods; PxL was evaluated by an alkylamine reaction with peroxides. While AC assays were unable to show positive effect of antioxidants (even 7–9% AC decrease was sometimes observed), AOB was able to highlight very well the expected improvement of serum antioxidant status (ranging from +22% to +40%), thus showing reliability of the new approach whatever the kind of plant food antioxidants. This is consistent with the capability of AOB approach to simultaneously account for AC and for the AC fraction not directly measurable, as consumed to lower serum oxidation status.

The introduction of antibiotics to treat bacterial infections either by killing or blocking their growth has been accompanied by the studies of mechanism that allows the drugs to kill the bacteria or to stop their proliferation. In such a scenario, the emergence of antibacterial agents active on the bacterial cell wall has been of fundamental importance in the fight against bacterial agents responsible for severe diseases. As a matter of fact, the cell wall, which plays many roles during the lifecycle, is an essential constituent of most bacteria. This overview focuses on the intracellular steps of peptidoglycan biosynthesis and the research of new antibacterial agents based on the enzymes involved in these early steps of the formation of cell membrane components.

α-Alkyl-α-aryl (trimethyltin) nitriles react spontaneously with aldehydes and ketones in THF/toluene to give β-hydroxy nitriles with satisfactory to good yields and diastereoselectivity. No extra catalyst is required in this aldol-like reaction. A possible trimethyltin-substituted ketene imine intermediate is invoked as reactive species. DFT calculations offer good support for this hypothesis.

Preparation of piperidine-2-one scaffolds by the hetero-Diels-Alder (HAD) reaction, assisted by microwaves, is described. The versatility of this new approach has been demonstrated by the synthesis of racemic (+/-)-2-phenylpiperidine. Theoretical calculations have allowed us to clarify the factors that govern ring closure to form four-membered rings, arising from a Staudinger-type electrocyclization, and/or six-membered rings through a classical [4+2] HAD cyclization. This competition may be lowered by increasing the electronic demand of the dienophile, as anticipated by the computational studies.

The review reports a short biography of the Italian naturalized chemist Hugo Schiff and an outline on the synthesis and use of his most popular discovery: the imines, very well known and popular as Schiff Bases. Recent developments on their "metallo-imines" variants have been described. The applications of Schiff bases in organic synthesis as partner in Staudinger and hetero Diels-Alder reactions, as "privileged" ligands in the organometallic complexes and as biological active Schiff intermediates/targets have been reported as well.

Reaction of a wide variety of aldehydes with the easily prepared 2-azadienes, in the presence of BF3 etherate, furnishes the corresponding hetero Diels–Alder adducts which have been converted, mainly, to cis epoxides via N-Boc protection followed by one-pot two-step ring opening and nucleophilic displacement of the halogen atom, resulting in final formation of an oxirane ring.

The enzyme α-glucosidase has attracted interest owing to its involvement in the digestive process of carbohydrate, its role in intracellular glycoprotein trafficking, tumorigenesis and viral infection. In this study, several members of a new family of N-heteroarylmethyl substituted azasugars were synthesized and evaluated as α-glucosidase inhibitors. We systematically investigated the effect of different N-substituents as well as the role of hydroxyl and carboxylate moieties on the piperidine ring. The compounds N-heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid emerged as potent α-glucosidase inhibitors. Unlike Acarbose and other clinically relevant α-glucosidase inhibitors, these compounds act through a reversible uncompetitive mechanism of inhibition which make them attractive candidates for drug development.

A catalyst-free method for the amidation of N-trimethylsilyl ketene imines using isocyanates is reported. A working hypothesis on the reaction pathway includes silatropism from the ketene nitrogen to the isocyanate oxygen as the driving force of the process.

The introduction of antibiotics to treat bacterial infections either by killing or blocking their growth has been accompanied by the development of resistance mechanism that allows the bacteria to survive and proliferate. In particular the successive series of β- lactams have selected several generations of β-lactamases including ESBLs, AmpC β-lactamases, KPC carbapenamases in Enterobacteriaceae, the metallo β-lactamases VIMs and IMPs, and very recently the threatening NDM-1 that confers resistance to virtually any clinically used antibiotic. The increasing use of carbapenems due to the spread of resistance to other existing antibacterial agents has facilitated the spread of resistance, especially in Acinetobacter spp. due to OXA- and metallo-carbapenemases. The pharmaceutical industry, that abandoned this field at the end of the nineties, is now trying to recover by developing some novel β-lactam antibiotics and novel β- lactamase-inhibitors, the latter to be used in combination with new as well as seasoned β-lactam antibiotics. This article provides a survey of patent and scientific literature for β-lactamase inhibitors discovered in the period 2006-2010.

Enantiomerically pure 1,4-dihydropyridines are pre- pared taking advantage of magnesium nitride as a useful and conve- nient source of 'solid ammonia'. The products possess various substituents at carbons 3, 4 and 5 of the dihydropyridine moiety.

Microwave-assisted organic synthesis has been used for the cyclization of a monocyclic oxoamide to the corresponding bicyclic derivative via a Wittig-type coupling by means of phosphite reagents. The parameters influencing the reaction yields under microwave (dielectric heating) and classical conditions (convective heating) have been evaluated.

Hetero-Diels-Alder (HDA) methodology has been applied to the synthesis of Venlafaxine taking advantage of a novel MW-assisted transketalization and hydroxymethylation reaction.

Trimethyltin nitriles either generated in situ or introduced directly readily react with carbonyl compounds to yield β-hydroxynitriles.

The synthesis of 5-phenylthio-1,3-oxazinan-4-ones, through a hetero Diels–Alder strategy, is described. The cycloadducts thus prepared have been shown to be useful intermediates for the synthesis of 1,3-aminoalcohols, valuable intermediates in the preparation of biologically significant molecules, e.g., optically active Duloxetines and Fluoxetines. In the course of this elaboration a novel microwave assisted desulfurization reaction is reported.

A new route to enantiomerically pure (R)- and (S)-fluoxetine is described using a hetero Diels-Alder strategy.

New β-lactam antibiotics were obtained by coupling the cephalosporin Cefotaxime with monobactams in order to assess the possibility to enhance the cephalosporin activity through a synergistic dual-action mechanism. The activities were tested, in vitro, against a panel of selected bacteria. Preliminary results showed a light change in antibacterial activity when compared with that of the starting cephem counterpart.

Recent state of the art in microwave mediated organic synthesis is reported. The claimed athermal effect of microwave in speeding-up organic reaction with concomitant improvements of the yields is ...

Preparation and ring-closure of 2-dimethylaminomethylene-5-substituted-3-oxo-pent-4-enoic acid benzyl esters to dihydropyridine rings are efficiently and quickly carried out under solvent-free conditions in an open-vessel microwave system. The syntheses of 1,6-disubstituted-4-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid benzyl esters are reported.

Vitamin D deficiency is very common in elderly people. We investigated whether a diet contained 400 IU of vitamin D per day for 10 weeks could increase plasma levels of 25-hydroxyvitamin-D3, a good measure of body status for vitamin D. The study groups included 232 subjects, aged 65-74 years (114 men and 118 women), who were assigned at random into two groups: 98 participants in intervention group received a diet which included 400 IU of vitamin D, and 134 in control group were given a diet without the Vitamin D addition. At the conclusion of the study, the intervention group showed a 102.3% increase of 25(OH)D3 plasma levels (40.2 nmol/L to 81.3 nmol/L, p 0.05). The difference, also evaluated by Mantel-Haenszel estimate, at the end of study between two groups was highly significant (p < 0.0001). This suggest that a diet contained 400 IU/d of vitamin D could improve vitamin D status in elderly people. A daily intake of 400 UI of vitamin D with diet must be recommended for elderly people to prevent hypovitaminosis D and to reduce risks of bone loss and fracture.

An elevated level of total plasma homocysteine (tHcy) is considered to be a predictor of the mortality risk for all diseases. A high consumption of vegetables and citrus fruit, both good sources of folate, decreases the concentration of tHcy. We investigated if supplementation of concentrated fruit and vegetables is able to decrease tHcy concentrations. For this purpose, we used a product that is presently on the market, made up of fruit and vegetable powders. 26 subjects participated in a cross-over design intervention trial. At the end of the study, each participant received 2 capsules of fruit and 2 capsules of vegetables a day for 4 weeks and then acted his/her own control for another 4 weeks. Daily extract intake decreased plasma tHcy from an expected mean ± SD level of 12.71 ± 3.23 umol/L observed after the 28-day control period to 7.98 ± 1.70 umol/L, a difference of 4.73 ± 1.153 (p Elevated tHcy is a risk factor causally linked to chronic disease. The plasma tHcy concentration was decreased as a result of taking a powdered fruit and vegetable extract on a daily basis.

Lewis acid-catalyzed cyclization of 2-aza-3-trimethylsilytoxy-buta-1,3-diene is reported.. Stereochemical differences with the uncatalyzed cyclization are discussed.

Antimutagens and anticarcinogens are known to play an important role in decreasing damages induced by oxidants. In this study, we investigated the genotoxic and antimutagenic potential of two selenium compounds (sodium selenite: Na(2)SeO(3); seleno-DL-methionine: C(5)H(11)NO(2)Se) and Vitamins A and E in yeast cells of Saccharomyces cerevisiae. An oxidative mutagen (hydrogen peroxide (H(2)O(2)), HP) was chosen as positive control. We determined the enzymatic activities involved in the protection against oxidative damages (catalase: CAT; superoxide dismutase: SOD; glutathione peroxidase: GPx) in the cytosolic extract of yeast cells. The results demonstrated that selenium compounds exerted both mutagenic and antimutagenic effect at different concentrations. Antimutagenesis was evident both in stationary and in logarithmic phase cells. Catalase, SOD, and GPx were significantly increased in the presence of all the compounds assayed. Vitamins A (retinol) and E (alpha-tocopherol) did not have toxic or mutagenic action.

The reactions of 2-aza-3-trimethylsilyloxy-1,3-butadiene with carbonyl dienophiles are described. 2-Aza-1,3-butadienes participate as dienes in the [4+2] cycloaddition with aldehydes to afford perhydroxazin-4-ones in good yields. Experimental results, however, show that a Mukaiyama type two-step reaction must be taken into account. The cycloadducts obtained have proved to be useful intermediates in the synthesis of alpha -amino-beta -hydroxy acids. (C) 2001 Elsevier Science Ltd. All rights reserved.

An uncatalyzed aldol-type reaction of aromatic N-trimethylsilyl ketene imines with O-protected α-trialkylsilyloxy or α-benzyloxy aldehydes is reported. It is shown that N-trimethylsilyl ketene imines (SKIs) are essential for the success of this aldol-type reaction, and that almost complete control of stereochemistry in the formation of the stereocentre vicinal to the stereogenic centre present in the starting aldehyde is seen when these compounds are used. A very high syn stereoselectivity was observed at room temperature, and a reversal of stereoselectivity to favour the formation of the anti product may be achieved at low temperature. Preliminary theoretical calculations support the hypothesis that the aldol-type reaction is facilitated by the formation of a cyclic transition state, with concomitant silatropic migration from the ketene imine-nitrogen to the aldehyde oxygen. The catalyst-free aldol reaction has been applied to aromatic N-trimethylsilyl ketene imines bearing two different aromatic groups. In these reactions, the diastereoselectivity for the stereocentre arising from aldehyde sp2 carbon remained extremely high, but the stereoselectivity for the formation of the new quaternary stereocentre was unsatisfactory.

Microwave technique has been utilised in the preparation of β-keto esters. Two different procedures are described: transesterification of β-keto esters and ring opening of 2,2,6-trimethyl-1,3-dioxin-4-one.

Changing the protecting group in the glyoxylic acid derived ketene from benzyloxy to benzoyloxy provides a simple way of switching the diastereoselectivity of the substituents on the final β-lactam ring from cis to trans.

The Diels–Alder reaction of 3-silyloxy-2-azadiene with formaldehyde has been studied at the B3LYP/6-31G* level of theory and the role played by a Lewis acid evaluated. It is shown that the reaction is preferred when the Lewis acid coordinates to the aldehyde oxygen. This coordination allows for a concerted as well as a stepwise mechanism for the cyclization. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Ring-closure of 1,3-azadienes to β-lactam rings is efficiently and quickly carried out under solvent-free conditions in an open-vessel microwave system. The synthesis of N-tert -butyldimethylsilyl azetidinones is reported.

The introduction of aminic nitrogen in organic molecules has been achieved in many different ways, one of the most popular being the use of imines. The main disadvantage of these starting materials lies in the difficulty of synthesising and using imines of ammonia, due to their instability, which results in their tendency to trimerize, giving the corresponding triazine. Recently a new class of imines, the N-metalloimines, a stable form of the corresponding elusive imines of ammonia, has found very useful applications in the synthesis of nitrogen-containing organic compounds. This review will cover the syntheses and applications of N-(trialkylsilyl)imines. It is not intended to be a comprehensive review of the literature; rather it is intended to highlight novel and potentially useful applications. In this context, particular emphasis will be devoted to methodologies which could be easily scaled up to kilogram scale. The synthesis of important small-ring heterocycles such as aziridines, β-lactams, pyrrolin...

An analysis of 13C chemical shifts of quaternary carbons of 3,3′-, 3,4′- and 4,4′-dimethoxy-2,2′-bithiophenes indicates they can be a useful tool for the identification of the inter-ring junction type. UV spectra and theoretical calculations are used to perform a conformational analysis of the compounds. The results show that the compounds prefer a non-planar conformation in non-condensated phases. The reasons for this non-planarity of the dimers and the effect on related polymers are discussed.

The silyl ketimines, generated in situ from diarylmethane nitriles and TmsCl via lithiation, undergo a non-catalyzed reaction with isocyanates to give highly substituted malonamides in moderate yields.

Stereocontrol in the asymmetric phosphonylation of aldehydes via organophosphorous esters has been obtained starting from chiral aldehydes. The nature of the O-protecting group is crucial to obtain, in terms of diastereoselectivity and chemical yields, the best results. An ab initio molecular orbital study on 2-silyloxy propanal and MM2 studies on 2-alkoxy propanal show the existence of stable cyclic and acyclic conformers, which are presumably responsible for the high syn diastereoselectivity observed in the addition of non-metal carrying phosphites.

Stereocontrolled syntheses of 4-methoxy trinem 2 and its enantiomer 3 were achieved using the ester enolate N -trimethylsilylimine approach. The key step was the resolution of racemic enolphosphates derived from ephedrine.

New conditions for the Staudinger reaction provide N -unsubstituted-3-phthalimido-β-lactams in satisfactory yields with complete trans-selectivity.

The four stereoisomers of phosphothreonine are obtained in high diastereomeric purity based on the stereoselective addition of trimethylsilyldiethylphosphite (TMSDEP) to scalemic N -trimethylsilyl-lacticimine and addition of TMSDEP to lactaldehyde followed by Mitsunobu inversion of the corresponding α-hydroxy-β-silyloxy phosphonate.

The azetidinone 14 , a key intermediate in the synthesis of novel tribactam antibiotics ( e.g. 2 ) was obtained via condensation of an ester enolate with a N -trimethylsilylimine.

Highly efficient chiral ester enolate-imine condensation, giving 3,4-disubstituted β-lactams with excellent trans-syn or trans-anti diastereoselectivity, is reported. The chiral information is included in the electrophilic partner of the condensation, nominally chiral α-, β-silyloxy- or alkoxy-N-trimethylsilyl-imines. The high diastereofacial selectivity is determined by the correct choice of the metal cations present in the reaction medium and the very nature of the hydroxy protecting group. By this procedure a number of azetidinones, intermediates in the synthesis of commercially interesting β-lactam antibiotics have been obtained. Fully assigned 1H and 13C NMR spectra of the so obtained azetidinones are reported.

The practical application of previously published thin-layer chromatographic (TLC) methods to polyphosphate detection in seafood was determined. Exogenous polyphosphates are distinguishable from naturally occurring phosphates by using TLC; their detection can be enhanced by sampling techniques. Polyphosphates will eventually hydrolyze to monophosphates and make detection virtually impossible. Hydrolysis and therefore, nondetection, is accelerated by certain commercial practices. Results indicate that TLC detection of added phosphates can be used as an inspection tool for fresh products and for frozen products stored about 1 year.

The title compound is obtained in high diastereomeric purity based on the stereoselective addition of trimethylsilyldibenzylphosphite (TMSDBP) to O-triisopropylsilyloxy(S)-lactaldehyde.

A preliminary study on the influence of the nitrogen substituent on the electrophilicity of the iminic carbon by evaluation of its 13 C chemical shift is reported. Two series of N -substituted imines, derived from benzaldehyde and lactic aldehyde and bearing, directly linked to the nitrogen, Al, Si, B, C, S, N, O groups, are examined. The dependence of 13 C iminic chemical shift is shown to be a function of mesomeric interaction and frontier orbital energetic factors as emphasized by ab initio calculations.

Enantioselective synthesis of active isocephem 1 was accomplished employing as key-step the cycloaddition reaction of N -trimethylsilylimine of O -protected lactic aldehyde ( 4 ) and cyclic silyl derivative of glycine ( 2 ). The elaboration of hydroxyethyl side chain was carried out by functional group interchange (FGI) of the hydroxyl group by a thioacetoxy group, and finally six-membered ring assembly followed by attachment of necessary appendage to N -7 nitrogen atom.

Protozoan parasites of the Leishmania genus are the causative agents of important diseases in humans and animals. During their life cycle in vertebrate hosts, protozoa are able to live and proliferate within phagolysosomes of host phagocytic cells. The capacity to live in this hostile environment is likely due to the cell surface glycoconjugate expression. In particular, lipophosphoglycan (LPG), a major surface glycoconjugate of Leishmania promastigotes, has been reported to play an active role in protecting parasites within phagolysosomes via the impairment of killing mechanisms. In this review, the authors emphasize some novel LPG-mediated escape mechanisms of promastigotes from human phagocyte responses, such as the impairment of oxidative burst and of chemotactic activity. In the light of these findings, the knowledge of biological actions of LPG may be useful in order to prepare a vaccine against human leishmaniasis, using LPG defective avirulent mutant strains.

The title compound is obtained in high diastereomeric purity based on the stereoselective addition of trimethylsilylphosphite to N-trimethylsilylimine of (S) lactic aldehyde.

The utility of the weak base potassium tert-butoxide has been success- fully demonstrated in the synthesis of β-lactams and 3,4-dihydropyri- din-2-ones starting from esters and imines

Magnesium nitride is used as ammonia source for the Hantzsch synthesis of 1,4-dihydropyridines such as (III) having chiral alcohols in the ester functionality.

The N-Aluminium imines derived from cyanohydrins have been used in the synthesis of α-amino alcohols with high diastereoselectivity.

Optically active 3,4-disubsutituted azetidin-2-ones have been prepared by annelation of chiral silylimines derived from (S) or (R)-lactaldehyde with the ester enolate of the ethyl 2,2,5,5,-tetramethyl-1,2,5-azadisilolidin-1-acetate (STABASE). Oxidation of the hydroxyethyl side chain on the C-4 position of the β-lactam ring, followed by Baeyer-Villiger oxidation led to the optically active (3S, 4S ) 3-amino-4-acetoxy-β-laclam. The absolute configuration of this compound was determined by elaboration of this substrate to a key intermediate in the synthesis of the antibiotic “Aztreonam”. Nucleophilic displacement of the acetoxy group led to optically active 3-amino-4-alkyl (aryl)-azetidin-2-ones.