Sensomics-Based Molecularization of the Taste of Pot-au-Feu, a Traditional Meat/Vegetable Broth.

Targeted quantification of 49 basic taste-active molecules, followed by the calculation of dose-over-threshold (DoT) factors, and taste re-engineering experiments revealed minerals, nucleotides/nucleosides, amino acids, organic acids, and carbohydrates as the key compounds of Pot-au-Feu, a traditional broth preparation from beef cuts and vegetables. Moreover, the dipeptide carnosine was identified to be the key inducer for the white-meaty and thick-sour orosensation of the broth, next to anserine and 1-deoxy-d-fructosyl-N-ß-alanyl-l-histidine, the latter of which has been identified for the first time by means of a sensory-guided fractionation. Sensory studies revealed the threshold concentration of carnosine in model broth to decrease by a factor of 5 upon nonenzymatic glycosylation to reach 4.4 mmol/L for its Amadori product 1-deoxy-d-fructosyl-N-ß-alanyl-l-histidine.

Impact of boiling conditions on the molecular and sensory profile of a vegetable broth.

Low-pressure cooking has recently been identified as an alternative to ambient and high-pressure cooking to provide food with enhanced organoleptic properties. This work investigates the impact of the cooking process at different pressures on the molecular and sensory profile of a vegetable broth. Experimental results showed similar sensory and chemical profiles of vegetable broths when boiling at 0.93 and 1.5 bar, while an enhancement of sulfur volatile compounds correlated with a greater leek content and savory aroma was observed when boiling at low pressure (80 °C/0.48 bar). Thus, low-pressure cooking would allow preserving the most labile volatiles likely due to the lower water boiling temperature and the reduced level of oxygen. This study evidenced chemical and sensory impact of pressure during cooking and demonstrated that the flavor profile of culinary preparations can be enhanced by applying low-pressure conditions.

Glycerol, an underestimated flavor precursor in the Maillard reaction.

The objective of the present work was to investigate in depth the role of glycerol in Maillard reactions and its potential to act as an active flavor precursor. Reactions using isotopically labeled compounds (various reducing sugars, proline, and glycerol) unambiguously demonstrated that, in addition to its role of solvent, glycerol actively contributes to the formation of proline-specific compounds in Maillard model systems. Additionally, rhamnose and fucose/proline/glycerol systems generated the 2-propionyl-1(3),4,5,6-tetrahydropyridines, known for their roasty, popcorn aroma. Their formation from such systems is unprecedented. The results presented here have direct implications for flavor generation during thermal processing of foods containing glycerol, which is a ubiquitous food ingredient and an underestimated flavor precursor.

Epicatechin B-ring conjugates: first enantioselective synthesis and evidence for their occurrence in human biological fluids.

Herein, the first enantioselective total synthesis of a number of biologically relevant (-)-epicatechin conjugates is described. The success of this synthesis relied on (i) optimized conditions for the stereospecific cyclization step leading to the catechin C ring; on (ii) efficient conjugation reactions; and on (iii) optimized deprotection sequences. These standard compounds have been subsequently used to elucidate for the first time the pattern of (-)-epicatechin conjugates present in four different human biological fluids following (-)-epicatechin absorption.

Elucidation of (-)-epicatechin metabolites after ingestion of chocolate by healthy humans.

After absorption in the gastrointestinal tract, (-)-epicatechin is extensively transformed into various conjugated metabolites. These metabolites, chemically different from the aglycone forms found in foods, are the compounds that reach the circulatory system and the target organs. Therefore, it is imperative to identify and quantify these circulating metabolites to investigate their roles in the biological effects associated with (-)-epicatechin intake. Using authentic synthetic standards of (-)-epicatechin sulfates, glucuronides, and O-methyl sulfates, a novel LC-MS/MS-MRM analytical methodology to quantify (-)-epicatechin metabolites in biological matrices was developed and validated. The optimized method was subsequently applied to the analysis of plasma and urine metabolites after consumption of dark chocolate, an (-)-epicatechin-rich food, by humans. (-)-Epicatechin-3'-ß-d-glucuronide (C(max) 290 ± 49 nM), (-)-epicatechin 3'-sulfate (C(max) 233 ± 60 nM), and 3'-O-methyl epicatechin sulfates substituted in the 4', 5, and 7 positions were the most relevant (-)-epicatechin metabolites in plasma. When plasmatic metabolites were divided into their substituent groups, it was revealed that (-)-epicatechin glucuronides, sulfates, and O-methyl sulfates represented 33 ± 4, 28 ± 5, and 33 ± 4% of total metabolites (AUC(0-24)(h)), respectively, after dark chocolate consumption. Similar metabolites were found in urine samples collected over 24h. The total urine excretion of (-)-epicatechin was 20 ± 2% of the amount ingested. In conclusion, we describe the entire metabolite profile and its degree of elimination after administration of (-)-epicatechin-containing food. These results will help us understand more precisely the mechanisms and the main metabolites involved in the beneficial physiological effects of flavanols.

A physiologically based biodynamic (PBBD) model for estragole DNA binding in rat liver based on in vitro kinetic data and estragole DNA adduct formation in primary hepatocytes.

Estragole has been shown to be hepatocarcinogenic in rodent species at high-dose levels. Translation of these results into the likelihood of formation of DNA adducts, mutation, and ultimately cancer upon more realistic low-dose exposures remains a challenge. Recently we have developed physiologically based biokinetic (PBBK) models for rat and human predicting bioactivation of estragole. These PBBK models, however, predict only kinetic characteristics. The present study describes the extension of the PBBK model to a so-called physiologically based biodynamic (PBBD) model predicting in vivo DNA adduct formation of estragole in rat liver. This PBBD model was developed using in vitro data on DNA adduct formation in rat primary hepatocytes exposed to 1'-hydroxyestragole. The model was extended by linking the area under the curve for 1'-hydroxyestragole formation predicted by the PBBK model to the area under the curve for 1'-hydroxyestragole in the in vitro experiments. The outcome of the PBBD model revealed a linear increase in DNA adduct formation with increasing estragole doses up to 100 mg/kg bw. Although DNA adduct formation of genotoxic carcinogens is generally seen as a biomarker of exposure rather than a biomarker of response, the PBBD model now developed is one step closer to the ultimate toxic effect of estragole than the PBBK model described previously. Comparison of the PBBD model outcome to available data showed that the model adequately predicts the dose-dependent level of DNA adduct formation. The PBBD model predicts DNA adduct formation at low levels of exposure up to a dose level showing to cause cancer in rodent bioassays, providing a proof of principle for modeling a toxicodynamic in vivo endpoint on the basis of solely in vitro experimental data.

In vivo bioavailability, absorption, excretion, and pharmacokinetics of [14C]procyanidin B2 in male rats.

Procyanidins are important biologically active compounds, but the pathway and extent of absorption and metabolism are controversial. We conducted a mass balance study to evaluate the total radioactivity excreted in urine and feces after oral administration of [(14)C]procyanidin B2 to male rats (n = 5). Urine and feces were collected daily from 0 to 96 h. Absolute bioavailability of (14)C from [(14)C]procyanidin B2 was calculated as approximately 82% using the values for total urinary (14)C. A pharmacokinetic study measured total radioactivity in the blood (n = 9). Blood samples were collected at designated time intervals (0.5-24 h) after administration. Three treatments were used: 1) intravenous, 2) oral higher dose (21 mg/kg b.wt.), and 3) oral lower dose (10.5 mg/kg). Blood concentration of total (14)C reached a maximum at approximately 6 h after ingestion of [(14)C]procyanidin B2 (groups II and III), and area under the curve (AUC) was dependent on oral dose. After intravenous or oral administration the terminal half-lives were similar, whereas 8-fold larger values were obtained after oral dosing for total clearance and the apparent volumes of distribution. These pharmacokinetic differences explain the apparently lower (14)C bioavailability (8-11%) for [(14)C]procyanidin calculated from blood [AUC((0-24))] values. After oral administration of [(14)C]procyanidin B2, 63% was excreted via urine within 4 days. The data suggest that much of the parent compound administered orally is degraded by the gut microflora before absorption and that these microbial metabolites have a different distribution from the compounds circulating after the intravenous dose.

Iron- and ruthenium-Lewis acid catalyzed asymmetric 1,3-dipolar cycloaddition reactions between enals and diaryl nitrones.

The highly tuned, one-point binding cationic cyclopentadienyl-iron and -ruthenium complexes 1 and 2 that incorporate chiral bidentate pentafluoroaryl-phosphinite ligands selectively coordinate and activate alpha,beta-unsaturated carbonyl compounds towards asymmetric catalytic cycloaddition reactions with diaryl nitrones. The reaction gives isoxazolidine products in good yields, with complete endo selectivity and high enantioselectivity. The products are obtained as a mixture of regioisomers in ratios varying from 96:4 to 15:85. The regioselectivity correlates directly with the electronic properties of the nitrone. This is shown by the experimental and computational data.

Ruthenium-Lewis acid catalyzed asymmetric Diels-Alder reactions between dienes and alpha,beta-unsaturated ketones.

The complex [Ru(Cp)(R,R-BIPHOP-F)(acetone)][SbF(6)], (R,R)-1 a, was used as catalyst for asymmetric Diels-Alder reactions between dienes (cyclopentadiene, methylcyclopentadiene, isoprene, 2,3-dimethylbutadiene) and alpha,beta-unsaturated ketones (methyl vinyl ketone (MVK), ethyl vinyl ketone, divinyl ketone, alpha-bromovinyl methyl ketone and alpha-chlorovinyl methyl ketone). The cycloaddition products were obtained in yields of 50-90 % and with enantioselectivities up to 96 % ee. Ethyl vinyl ketone, divinyl ketone and the halogenated vinyl ketones worked best and their reactions with acyclic dienes consistently provided products with >90 % ee. alpha-Chlorovinyl methyl ketone performed better than alpha-bromovinyl methyl ketone. The reaction also provided a [4.3.1]bicyclic ring system in 95 % ee through an intramolecular cycloaddition reaction. Crystal structure determinations of [Ru(Cp)((S,S)-BIPHOP-F)(mvk)][SbF(6)], (S,S)-1 b, and [Ru(Cp)((R,R)-Me(4)BIPHOP-F)(acrolein)][SbF(6)], (R,R)-2 b, provided the basis for a rationalization of the asymmetric induction.

[CpRu((R)-Binop-F)(H2O)][SbF6], a new fluxional chiral Lewis acid catalyst: synthesis, dynamic nmr, asymmetric catalysis, and theoretical studies.

The C(2)-symmetric electron-poor ligand (R)-BINOP-F (4) was prepared by reaction of (R)-BINOL with bis(pentafluorophenyl)-phosphorus bromide in the presence of triethylamine. The iodo complex [CpRu((R)-BINOP-F)(I)] ((R)-6) was obtained by substitution of two carbonyl ligands by (R)-4 in the in situ-prepared [CpRu(CO)(2)H] complex followed by reaction with iodoform. Complex 6 was reacted with [Ag(SbF(6))] in acetone to yield [CpRu((R)-BINOP-F)(acetone)][SbF(6)] ((R)-7). X-ray structures were obtained for both (R)-6 and (R)-7. The chiral one-point binding Lewis acid [CpRu((R)-BINOP-F)][SbF(6)] derived from either (R)-7 or the corresponding aquo complex (R)-8 activates methacrolein and catalyzes the Diels-Alder reaction with cyclopentadiene to give the [4 + 2] cycloadduct with an exo/endo ratio of 99:1 and an ee of 92% of the exo product. Addition occurs predominantly to the methacrolein C(alpha)-Re face. In solution, water in (R)-8 exchanges readily. Moreover, a second exchange process renders the diastereotopic BINOP-F phosphorus atoms equivalent. These processes were studied by the application of variable-temperature (1)H, (31)P, and (17)O NMR spectroscopy, variable-pressure (31)P and(17)O NMR spectroscopy, and, using a simpler model complex, density functional theory (DFT) calculations. The results point to a dissociative mechanism of the aquo ligand and a pendular motion of the BINOP-F ligand. NMR experiments show an energy barrier of 50.7 kJ mol(-1) (12.2 kcal mol(-1)) for the inversion of the pseudo-chirality at the ruthenium center.

Crown-ether functionalised second coordination sphere palladium catalysts by molecular imprinting.

Functionalisation of the second coordination sphere of a molecularly imprinted Pd complex was achieved by localising within the polymeric cavity a crown-ether receptor capable of altering the catalytic activity of the reactive site.

Synthesis of C-3' methyl taxotere (docetaxel).

Protected (3R,4S)-N-Boc-3-hydroxy-4-methyl-4-phenylazetidin-2-one has been synthesized stereoselectively and used to esterify protected 10-desacetylbaccatin III to give, following removal of the protecting groups, novel C-3' methyl taxotere (docetaxel).

Iron and ruthenium Lewis acid catalyzed asymmetric 1,3-dipolar cycloaddition reactions between nitrones and enals.

The single coordination-site transition metal Lewis acids [CpM(BIPHOP-F)][SbF6] (M = Fe, Ru) catalyze the [3+2] dipolar cycloaddition reaction between reactive nitrones and alpha,beta-unsaturated aldehydes to give chiral isoxazolidines with ee values of 75 to >96%. The stereochemistry of the major enantiomer is consistent with an endo approach of the nitrone to the Calpha-Si-face of the enal in the s-trans conformation in the (R,R)-catalyst site. The absolute configuration is based on an X-ray structure determination.