Aziridine synthesis via nucleophilic attack of carbene equivalents on imines: the aza-Darzens reaction

The development of new methods for the efficient synthesis of aziridines has been of considerable interest to researchers for more than 60 years, but no single method has yet emerged as uniformly applicable, especially for asymmetric synthesis of chiral aziridines. One method which has been intensely examined and expanded of late involves the nucleophilic addition to imines by anions bearing a-leaving groups; by analogy with the glycidate epoxide synthesis, these processes are often described as "aza-Darzens reactions". This Microreview gives a summary of the area, with a focus on contemporary developments. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Asymmetric aziridine synthesis by aza-Darzens reaction of N-diphenylphosphinylimines with chiral enolates. Part 2: inversion of diastereoselectivity

The aza-Darzens ('ADZ') reactions of N-diphenylphosphinyl ('N-Dpp') imines with chiral enolates derived from N-bromoacetyl 2S-2,10-camphorsultam proceed in generally good yield to give N-diphenylphosphinyl aziridinoyl sultams. However, the stereoselectivity of the reaction is dependent upon the structure of the imine substituent: when the chiral enolate was reacted with arylimines substituted in the ortho-position, mixtures of cis- and trans-2'R,3'R-aziridines were obtained, often with a complete selectivity in favour of the trans-isomer. (c) 2006 Elsevier Ltd. All rights reserved.

Asymmetric aziridine synthesis by aza-Darzens reaction of N-diphenylphosphinylimines with chiral enolates. Part 1: formation of cis-aziridines

Theaza-Darzens ('ADZ') reactions off-diphenylphosphinyl (W-Dpp') imines with chiral enolates derived from oxazolidinones and camphorsultam have been Studied. Whilst oxazolidinone enolates reacted poorly in terms of aziridination, the use of the chiral enolate derived from both antipodes of N-bromoacetyl 2, 10-camphorsultam, 2R-(5) and 2S-(5), with N-diphehenylphosphinyl aryl and tert-butylimines proceeded in generally good yield to give, respectively, (2'R,3'R)- or (2'S,3'S)-cis-N-diphenylphosphinyl aziridinoyl sultams of high de. (c) 2006 Elsevier Ltd. All rights reserved.

A reaction surface Hamiltonian study of malonaldehyde

We report calculations using a reaction surface Hamiltonian for which the vibrations of a molecule are represented by 3N-8 normal coordinates, Q, and two large amplitude motions, s(1) and s(2). The exact form of the kinetic energy operator is derived in these coordinates. The potential surface is first represented as a quadratic in Q, the coefficients of which depend upon the values of s(1),s(2) and then extended to include up to Q(6) diagonal anharmonic terms. The vibrational energy levels are evaluated by solving the variational secular equations, using a basis of products of Hermite polynomials and appropriate functions of s(1),s(2). Our selected example is malonaldehyde (N=9) and we choose as surface parameters two OH distances of the migrating H in the internal hydrogen transfer. The reaction surface Hamiltonian is ideally suited to the study of the kind of tunneling dynamics present in malonaldehyde. Our results are in good agreement with previous calculations of the zero point tunneling splitting and in general agreement with observed data. Interpretation of our two-dimensional reaction surface states suggests that the OH stretching fundamental is incorrectly assigned in the infrared spectrum. This mode appears at a much lower frequency in our calculations due to substantial transition state character. (c) 2006 American Institute of Physics.

Evaluation of data for atmospheric models: master equation/RRKM calculations on the combination reaction, BrO+NO2 -> BrONO2, a conundrum

Experimental data for the title reaction were modeled using master equation (ME)/RRKM methods based on the Multiwell suite of programs. The starting point for the exercise was the empirical fitting provided by the NASA (Sander, S. P.; Finlayson-Pitts, B. J.; Friedl, R. R.; Golden, D. M.; Huie, R. E.; Kolb, C. E.; Kurylo, M. J.; Molina, M. J.; Moortgat, G. K.; Orkin, V. L.; Ravishankara, A. R. Chemical Kinetics and Photochemical Data for Use in Atmospheric Studies, Evaluation Number 15; Jet Propulsion Laboratory: Pasadena, California, 2006)(1) and IUPAC (Atkinson, R.; Baulch, D. L.; Cox, R. A.: R. F. Hampson, J.; Kerr, J. A.; Rossi, M. J.; Troe, J. J. Phys. Chem. Ref. Data. 2000, 29, 167) 2 data evaluation panels, which represents the data in the experimental pressure ranges rather well. Despite the availability of quite reliable parameters for these calculations (molecular vibrational frequencies (Parthiban, S.; Lee, T. J. J. Chem. Phys. 2000, 113, 145)3 and a. value (Orlando, J. J.; Tyndall, G. S. J. Phys. Chem. 1996, 100,. 19398)4 of the bond dissociation energy, D-298(BrO-NO2) = 118 kJ mol(-1), corresponding to Delta H-0(circle) = 114.3 kJ mol(-1) at 0 K) and the use of RRKM/ME methods, fitting calculations to the reported data or the empirical equations was anything but straightforward. Using these molecular parameters resulted in a discrepancy between the calculations and the database of rate constants of a factor of ca. 4 at, or close to, the low-pressure limit. Agreement between calculation and experiment could be achieved in two ways, either by increasing Delta H-0(circle) to an unrealistically high value (149.3 kJ mol(-1)) or by increasing , the average energy transferred in a downward collision, to an unusually large value (> 5000 cm(-1)). The discrepancy could also be reduced by making all overall rotations fully active. The system was relatively insensitive to changing the moments of inertia in the transition state to increase the centrifugal effect. The possibility of involvement of BrOONO was tested and cannot account for the difficulties of fitting the data.

Comparison of new microemulsion prepared "Pt-in-Ceria" catalyst with conventional "Pt-on-Ceria" catalyst for water-gas shift reaction

New "Pt-in-CeO2" catalyst prepared by microemulsion method is shown to give higher activity for a water-gas shift reaction but with no formation of CH4, the side product from hydrogenation of carbon oxides using a hydrogen-rich reformate as compared to conventional "Pt-on-CeO2" catalysts. Detailed characterization by DRIFT analysis and temperature programmed reduction presented in this work clearly suggest the ceria coverage on Pt inhibits the metal from forming a strong CO adsorption.

Metabolism of Maillard reaction products by the human gut microbiota: implications for health

The human colonic microbiota imparts metabolic versatility on the colon, interacts at many levels in healthy intestinal and systemic metabolism, and plays protective roles in chronic disease and acute infection. Colonic bacterial metabolism is largely dependant on dietary residues from the upper gut. Carbohydrates, resistant to digestion, drive colonic bacterial fermentation and the resulting end products are considered beneficial. Many colonic species ferment proteins but the end products are not always beneficial and include toxic compounds, such as amines and phenols. Most components of a typical Western diet are heat processed. The Maillard reaction, involving food protein and sugar, is a complex network of reactions occurring during thermal processing. The resultant modified protein resists digestion in the small intestine but is available for colonic bacterial fermentation. Little is known about the fate of the modified protein but some Maillard reaction products (MRP) are biologically active by, e.g. altering bacterial population levels within the colon or, upon absorption, interacting with human disease mechanisms by induction of inflammatory responses. This review presents current understanding of the interactions between MRP and intestinal bacteria. Recent scientific advances offering the possibility of elucidating the consequences of microbe-MRP interactions within the gut are discussed.

The reaction of flavonoid metabolites with peroxynitrite

There is much interest in the bioactivity of in vivo flavonoid metabolites. We report for the first time the hierarchy of reactivity of flavonoid metabolites with peroxynitrite and characterise novel reaction products. O-Methylation of the B-ring catechol containing flavonoids epicatechin and quercetin, and O-glucuronidation of all flavonoids reduced their reactivity with peroxynitrite. The reaction of the flavanones hesperetin and naringenin and their glucuronides resulted in the formation of multiple mono-nitrated and nitrosated products. In contrast, the catechol-containing flavonoids epicatechin and quercetin yielded oxidation products which when trapped with glutathione led to the production of glutathionyl-conjugates. However, the O-methylated metabolites of epicatechin yielded both mono-and di-nitrated products and nitrosated metabolites. The 3'-O-methyl metabolite of quercetin also yielded a nitrosated species, although its counterpart 4'-O-methyl quercetin yielded only oxidation products. Such products may represent novel metabolic products in vivo and may also express cellular activity. (c) 2006 Elsevier Inc. All rights reserved.

Reducing acrylamide precursors in raw materials derived from wheat and potato

A review of agronomic and genetic approaches as strategies for the mitigation of acrylamide risk in wheat and potato is presented. Acrylamide is formed through the Maillard reaction during high-temperature cooking, such as frying, roasting, or baking, and the main precursors are free asparagine and reducing sugars. In wheat flour, acrylamide formation is determined by asparagine levels and asparagine accumulation increases dramatically in response to sulfur deprivation and, to a much lesser extent, with nitrogen feeding. In potatoes, in which sugar concentrations are much lower, the relationships between acrylamide and its precursors are more complex. Much attention has been focused on reducing the levels of sugars in potatoes as a means of reducing acrylamide risk. However, the level of asparagine as a proportion of the total free amino acid pool has been shown to be a key parameter, indicating that when sugar levels are limiting, competition between asparagine and the other amino acids for participation in the Maillard reaction determines acrylamide formation. Genetic approaches to reducing acrylamide risk include the identification of cultivars; and other germplasm in which free asparagine and/or sugar levels are low and the manipulation of genes involved in sugar and amino acid metabolism and signaling. These approaches are made more difficult by genotype/ environment interactions that can result in a genotype being "good" in one environment but "poor" in another. Another important consideration is the effect that any change could have on flavor in the cooked product. Nevertheless, as both wheat and potato are regarded as of relatively high acrylamide risk compared with, for example, maize and rice, it is essential that changes are achieved that mitigate the problem.

The reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth

Studies have suggested that diets rich in polyphenols Such as flavonoids may lead to a reduced risk of gastrointestinal cancers. We demonstrate the ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D I levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract. (c) 2005 Elsevier Inc. All rights reserved.

The use of dead-end and cross-flow nanofiltration to purify prebiotic oligosaccharides from reaction mixtures

Nanofiltration (NF) of model sugar solutions and commercial oligosaccharide mixtures were studied in both dead-end and cross-flow modes. Preliminary trials, with a dead-end filtration cell, demonstrated the feasibility of fractionating monosaccharides from disaccharides and oligosaccharides in mixtures, using loose nanofiltration (NF-CA-50, NF-TFC-50) membranes. During the nanofiltration purification of a commercial oligosaccharide mixture, yields of 19% (w w-1) for the monosaccharides and 88% (w w-1) for di, and oligosaccharides were obtained for the NF-TFC-50 membrane after four filtration steps, indicating that removal of the monosaccharides is possible, with only minor losses of the oligosaccharide content of the mixture. The effects of pressure, feed concentration, and filtration temperature were studied in similar experiments carried out in a cross-flow system, in full recycle mode of operation. The rejection rates of the sugar components increased with increasing pressure, and decreased with both increasing total sugar concentration in the feed and increasing temperature. Continuous diafiltration (CD) purification of model sugar solutions and commercial oligosaccharide mixtures using NF-CA-50 (at 25oC) and DS-5-DL (at 60oC) membranes, gave yield values of 14 to 18% for the monosaccharide, 59 to 89% for the disaccharide and 81 to 98% for the trisaccharide present in the feed. The study clearly demonstrates the potential of cross flow nanofiltration in the purification of oligosaccharide mixtures from the contaminant monosaccharides.

Rapid quality assessment of wheat cultivars registered in Poland using the 2-g mixograph and multivariate statistical analysis

Baking and 2-g mixograph analyses were performed for 55 cultivars (19 spring and 36 winter wheat) from various quality classes from the 2002 harvest in Poland. An instrumented 2-g direct-drive mixograph was used to study the mixing characteristics of the wheat cultivars. A number of parameters were extracted automatically from each mixograph trace and correlated with baking volume and flour quality parameters (protein content and high molecular weight glutenin subunit [HMW-GS] composition by SDS-PAGE) using multiple linear regression statistical analysis. Principal component analysis of the mixograph data discriminated between four flour quality classes, and predictions of baking volume were obtained using several selected mixograph parameters, chosen using a best subsets regression routine, giving R-2 values of 0.862-0.866. In particular, three new spring wheat strains (CHD 502a-c) recently registered in Poland were highly discriminated and predicted to give high baking volume on the basis of two mixograph parameters: peak bandwidth and 10-min bandwidth.