Piotr Krajewski

Strategies for the Formation of 1-Dethia-1-oxa-cephams

Abstract The paper describes three possible routes for the formation of 1-dethia-1-oxa-cephams. The first two routes: (a) [2+2]cycloaddition to chiral vinyl ethers and (b) condensation of 4-acetoxyazetidin-2-one to chiral alcohols, are followed by the ring closure step involving N-alkylation. The third route (c) consists of N-alkylation prior to the cyclization step. In order to compare routes (a), (b) and (c), diastereomeric 1-dethia-3-(4-methoxybenzyloxy)-1-oxacephams were synthesized using three possible strategies. While the comparison of stereoselectivities of the [2+2]cycloaddition method (a) and the condensation (b) shows unequivocally the advantage of the former, the route (c) leads to the reverse direction of asymmetric induction relative to the first two steps and offers the highest asymmetric induction.

17O chemical shifts and deuterium isotope effects on 13C chemical shifts of intramolecularly hydrogen-bonded compounds

17O chemical shifts were measured in 40 enamines activated in the β‐position by C=O, COO, NO2, SO and SO2 groups. Data for the oxygen‐containing series of o‐hydroxyacyl aromatics are also included for comparison. Intramolecular hydrogen bonding in the enamines is discussed in terms of the acceptor and donor groups and the separating link. 17O chemical shifts, the two‐bond deuterium isotope shifts on C‐α 13C shifts and 1H NH or OH chemical shifts are correlated to show the interrelations of these parameters in elucidating intramolecular hydrogen bonds and their strength in a wide variety of compounds. 17O chemical shifts in open‐chain compounds are shown to reflect intramolecular hydrogen bonding by a change to lower frequency whereas for five‐membered rings steric effects cause higher frequency chemical shifts.

The tautomeric equilibrium and stereochemistry of β-sulfonyl enamines

Compounds of three groups of parent secondary aliphatic β-sulfonyl enamines, unsubstituted or with an alkyl substituent in the α or β positions, have been studied. The β-sulfonyl enamines are found in equilibria between the E and Z enamine and imine forms in varying amounts in CDCl3 solution. 1H, 13C and 15N data were acquired and used for the assignment of the three species in solution. Considerable variations in the amounts of enamine E and Z and imine forms are found, depending on the substitution pattern. The conformational space of the equilibrated tautomers have been investigated using steady-state NOE experiments, dynamic NMR and nJ(H,H) and nJ(C,H) long-range spin-spin coupling constants, as well as ab initio HF and DFT calculations for structure determination and relative energy evaluations. Based on NOE, saturation transfer experiments and conformational analysis, an equilibrium scheme is proposed showing the mechanism and the involvement of water in the transformation of β-sulfonyl imines into the corresponding enamines.

Solution conformation of the alkaloid chelidonine and its protonated form

The solution conformation of the alkaloid chelidonine in CDCl3 was studied by proton steady‐state NOE and DPFGSE NOE techniques. The experiments showed that the molecule adopts in solution essentially the same conformation as in the crystal state. Upon protonation with trifluoroacetic acid in CDCl3 chelidonine preserves its conformation, although a strong intramolecular N+HO hydrogen bond is formed. Conformational searches in vacuo performed with the use of GMMX software strongly suggest that the molecular geometry in the crystal state of chelidonine is also the global energetic minimum of the molecule. Copyright

Towards stereochemical and conformational assignment in flexiblemolecules using NOEs and molecular modelling

The title methods are used firstly to assign the relative stereochemistry of the four diastereomers of a 2,3-dihydrobenzofuran derivative, and secondly to define the preferred conformation of one diastereomer. The experimental constraints are obtained from steady-state NOE measurements and coupling constants, and are compared to calculated values using low-energy conformations calculated using the molecular mechanics program PCMODEL. The significance of the results is assessed by using a statistical analysis, based on an estimation of the magnitude of experimental errors, which produced the correct relative stereochemistries, showed that the experimental data are not fitted by any single conformation, and generated a preferred conformation which is very similar to that found in an X-ray structure. The method can give information on the relative stereochemistry of chiral centres several bonds apart.

Stereochemical model of [2+2]cycloaddition of chlorosulfonyl isocyanate to chiral vinyl ethers

A comparison of steady-state NOE coefficients measured for vinyl-substituted isopropyl ethers with conformations generated by a molecular mechanics program allowed a characterization of the most favorable ground state conformations. With high confidence it was possible to assign the lowest energy conformation to one which is characterized by a diastereo-zeroplane consisting of the s-trans vinyl group, the stereogenic center and the methyl group (Fig. 3). A stereochemical model of the transition state for [2+2]cycloaddition of chlorosulfonyl isocyanate and vinyl ethers is proposed, based on the lowest energy conformation derived from NOE coefficients, which agrees well with the experimental facts and provides a sound explanation of the direction of asymmetric induction.

A simple method for the assignment of the relative stereochemistry of 2-substituted clavams

Bentley and Hunt’s empirical rule for the determination of the anti/syn relationship of protons attached to C-2 and C-5 atoms in 2-substituted clavams does not predict the correct stereochemistry in a series of 2-substituted clavams synthesised by us. In this paper we propose a simple method for determination of the relative stereochemistry of 2-substituted clavams based on nuclear Overhauser effect (NOE) experiments and assignment of the diastereotopicity of protons attached to the C-3 atom. Circular dichroism (CD) measurements and X-ray crystallography provide stereochemical and spectral assignments.

Does a Progressive PIT Stabilize the Economy? A Comparison of Progressive and Flat Taxes

Abstract The aim of the article is to examine the impact of progressive personal income tax rates and the effectiveness of this tax as an automatic economic stabilizer. The assessment of automatic stabilizers is based on the estimates of tax cyclical components. The study shows that the output elasticity of PIT is higher than one, which means that the analysed tax acts relatively efficiently as an automatic stabilizer. However, it was also observed that the tax progressivity is not the main reason of the effectiveness of a progressive PIT as an automatic stabilizer. The study shows that changes in progressive rates of PIT, contrary to widespread opinions, have little effect on the effectiveness of passive fiscal policy. Personal income tax acts as automatic stabilizer mostly due not to the progressive tax rates, but because of the sensitivity of employment to GDP fluctuations.

The Effectiveness of Fiscal Policy Over the Business Cycle: A CEE Perspective

ABSTRACT In this article we analyze the effectiveness of fiscal policy—for a group of four Central and Eastern European countries. The recent literature shows that fiscal multipliers in the developed economies are higher during recession than expansion. So far, similar empirical analyses have been lacking for CEE countries. The results presented in this article show that fiscal multipliers in CEE countries differ with respect to the phase of the business cycle. Based on the SVAR methodology in which we allow for deterministic regime switching, we show that the government spending multipliers are significantly higher when the output gap is negative.

Comparison of Nominal and Real Rigidities: Fiscal Policy Perspective

Abstract This paper examines the impact of nominal and real rigidities in the economy on the effects of fiscal policy. The study confirmed the hypothesis that both nominal and real rigidities enhance the impact of fiscal policy on the Polish economy. In the case of nominal price rigidity it was found that the impact of government spending on GDP depends on the conduct of monetary policy. On the other hand, under conditions of wage rigidity, the strength of fiscal multipliers depends on the slope of the labour supply curve. The study also examined two types of real rigidities - lack of access to the credit market, and consumer habits. Analyses show that the above rigidities result primarily in a strong positive relationship between government spending and the level of consumption Streszczenie W pracy zbadano wpływ występowania sztywności nominalnych i realnych w gospodarce na charakter oddziaływania polityki fiskalnej. Potwierdzono hipotezę, że zarówno sztywności nominalne, jak i realne zwiększają siłę wpływu polityki fiskalnej na gospodarkę polską. W przypadku sztywności nominalnej cen uzyskano, że siła oddziaływania wydatków rządowych na PKB uzależniona jest od prowadzonej polityki pieniężnej. Natomiast w warunkach sztywności płac wysokość mnożników fiskalnych zależy od nachylenia krzywej podaży pracy. W pracy zbadano również dwa rodzaje sztywności realnych - brak dostępu do rynku kredytowego i występowanie przyzwyczajeń konsumpcyjnych. Z przeprowadzonych analiz wynika, że ww. sztywności skutkują przede wszystkim silną dodatnią zależnością pomiędzy wydatkami rządowymi a poziomem konsumpcji.