Regioselective cycloaddition of 3-azatrienes with enamines. Synthesis of pyridines derived from β-aminoacids

Aza-Wittig reaction of N-vinylic phosphazenes with α,β-unsaturated aldehydes leads to the formation of 3-azatrienes through a [2+2]-cycloaddition-cycloreversion process. Subsequent, regioselective [4+2]-cycloaddition of 3-azatrienes with pyrrolidinocycloalkanone affords bicyclic dihydropyridines and pyridines in a regioselective fashion. 2-Heterodiene moiety of azatriene is involved in the formation of the six-membered ring skeleton of pyridine derivatives.     

Study of the interaction of structurally similar bioactive compounds by thin-layer chromatography

The interaction between steroids and cholesterol is studied by reversed-phase thin-layer chromatography (TLC) using TLC plates impregnated by cholesterol and methanol-water mixtures as the eluents. The R(M) values obtained are in linear correlation with the methanol concentration of the eluent. The slope obtained from the linear regression analysis, which is characteristic of the strength of interaction, is determined. Stepwise regression and principal component analysis are carried out to find a relationship between the physicochemical parameters of steroid drugs and the strength of the interaction, which is followed by nonlinear mapping and cluster analysis to visualize the obtained results. The results show that steric and electronic parameters of the steroid drugs have a significant effect on the strength of the interaction between these structurally similar molecules.     

Mechanism and kinetics of the reaction of OH radicals with glyoxal and methylglyoxal: a quantum chemistry + CVT/SCT approach.

A theoretical study of the mechanism and kinetics of the OH hydrogen abstraction from glyoxal and methylglyoxal is presented. Optimum geometries, frequencies, and gradients have been computed at the BHandHLYP/6-311++G(d,p) level of theory for all the stationary points, as well as for 12 additional points along the minimum energy path (MEP). Energies were obtained by single-point calculations at the above geometries using CCSD(T)/ 6-311++G(d,p) to produce the potential energy surface. The rate coefficients were calculated for the temperature range 200-500 K by using canonical variational theory (CVT) with small-curvature tunneling (SCT) corrections. Our analysis suggests a stepwise mechanism, which involves the formation of a reactant complex. The overall agreement between the calculated and experimental kinetic data is very good. This agreement supports the reliability of the Arrhenius parameters of the glyoxal + OH reaction that are proposed in this work for the first time. The Arrhenius expressions that best describe the studied reactions are k1 = (9.63 +/- 0.23) x l0(-13)exp[(517 +/- 7)/T] and k2 = (3.93 +/- 0.11) x 10(-13)exp[(1060 +/- 8)/T]cm3 molecule(-1)s(-1) for glyoxal and methylglyoxal, respectively.     

Could ionic gamma-elimination be concerted: clocking the internal displacement across a cyclobutane ring

Carbanion 1, obtained by a nucleophilic attack of PhSe- on 3-chlorobicyclobutane-carbonitrile in DME undergoes both protonation and elimination as shown in eq 1. Alcohols of increasing acidity in the following order: t-BuOH, i-PrOH, MeOH, trifluoroethanol (TFE), and hexafluoro2-propanol (HFIP) were used as proton donors. An Eigen-type plot of the log of the product ratio (protonation/elimination) vs the pK(a) of the alcohols, levels off for the two most acidic alcohols, TFE and HFIP which react at a diffusion-controlled rate. The partitioning of the products between protonation and elimination enables, therefore, the determination of the rate constant for the internal elimination as approximately 3 x 10(10) s(-1). Ab initio calculations at the B3LYP/6-31G level show that the elimination from a model carbanion (4, eq 4) occurs in a barrierless process. Simulation of the experimental reaction by including solvation effects using the Onsager model, shows that using the dielectric constant of DME (7.2) stabilizes, as expected, the carbanion and prevents a spontaneous elimination. In the absence of solvation effects, using Me- as a base, a complete elimination of HCl (proton removal and leaving-group expulsion) took place from 3-chlorocyclobutanecarbonitrile in a barrierless process without the formation of any discrete intermediate.     

Retention characteristics and practical applications of carbon sorbents

Reversed-phase separations provides a versatile technique in high-performance liquid chromatography. Porous graphitized carbon (PGC) support shows unique retention characteristics. Separations on PGC columns use typical reversed-phase eluents (water and organic modifiers miscible with water), however, the retention order of solutes generally does not follow their hydrophobicity order. Molecular hydrophobicity influences but not determines the elution order of any set of solutes. The properties of these supports, mechanisms of retention and application are discussed, along with correlations which can guide the choice of solvent combinations for typical separations.     

Panicutin,ein neues Alkaloid aus Aconitum paniculatum LAM. 4. Mitteilung über Aconitum

Panicutin, a New Alkaloid from Aconitum paniculatum LAM. A new diterpene alkaloid, which we named panicutine ( 2 ), was isolated from the paniculatine-containing chemovariety of Aconitum paniculatum LAM. Investigation by spectral methods showed that 2 has the formula C₂₃H₂₉N₄₄ and belongs to the hetidine ( 1 )-type alkaloids. It has one acetoxy group at C(2) and one carbonyl group each at C (6) and C (11).     

Brønsted acid catalyzed enantioselective α-amidoalkylation in the synthesis of isoindoloisoquinolines

The Parham cyclization-intermolecular α-amidoalkylation sequence results in the facile enantioselective synthesis of 12b-substituted isoindoloisoquinolines (ee up to 95%) using BINOL-derived Br?nsted acids. α-Amidoalkylation of indole occurs through the formation of a chiral conjugate base/bicyclic quaternary N-acyliminium ion pair.     

Parham-type cycliacylation with Weinreb amides. Application to the synthesis of fused indolizinone systems

[reaction: see text] Weinreb amides behave as efficient internal electrophiles in Parham-type cycliacylation reactions. Thus, aryl- and heteroaryllithiums generated by lithium-halogen exchange undergo intramolecular cyclization to give fused indolizinone systems as pyrrolo[1,2-b]isoquinolines, thieno[2,3-f]indolizinones, and pyrrolo[1,2-b]acridinones in high yields.     

Biological matrices for the evaluation of exposure to environmental tobacco smoke during prenatal life and childhood

The measurement of nicotine and its major metabolites cotinine and trans-3´-hydroxicotinine together with other minor metabolites (e.g., cotinine N-oxide, cotinine, and trans-3´-hydroxicotinine glucuronides) in conventional and nonconventional biological matrices has been used as a biomarker to assess the exposure to environmental tobacco smoke during childhood. The determination of these substances in matrices such as amniotic fluid, meconium, and fetal hair accounts for prenatal exposure to cigarette smoking at different stages of pregnancy. Nicotine and its metabolites in cord blood, neonatal urine, and breast milk are useful for determining acute exposure to drugs of abuse in the period immediately before and after delivery. Cotinine measurement in children’s blood and urine and nicotine and cotinine measurements in children’s hair constitute objective indexes of acute and chronic exposure during infancy, respectively. However, for monitoring and categorizing cumulative exposure to environmental tobacco smoke during the entire childhood, including the prenatal period, the assessment of nicotine in teeth has been proposed as a promising noninvasive tool. This article reviews the usefulness of measurement of nicotine and its metabolites in different fetal and pediatric biological matrices in light of noninvasive collection, time window of exposure detection, and finally clinical application in pediatrics.