Crystallographic and spectroscopic study on a known orally active progestin

6,17a-dimethyl-4,6-pregnadiene-3,20-dione (medrogestone, 2) is for a long time known steroid endowed with progestational activity. In order to study its crystallographic and NMR spectroscopic properties with the aim to fill the literature gap, we prepared medrogestone following a traditional procedure. A careful NMR study allowed the complete assignement of the 1H and 13C NMR signals not only of medrogestone but also of its synthetic intermediates. The structural and stereochemical characterizations of medrogestone togheter with its precursor 17a-methyl-3-ethoxy-pregna-3,5- dien-20-one were described by means of X-ray analysis, allowing a deepened conformational investigation

Crystallographic and NMR Investigation of Ergometrine and Methylergometrine, Two Alkaloids from Claviceps purpurea

Ergometrine and methylergometrine are two alkaloids that are used as maleate salts for the prevention and control of postpartum hemorrhage. Although the two molecules have been known for a long time, few and discordant crystallographic and NMR spectroscopic data are available in the literature. With the aim of providing more conclusive data, we performed a careful NMR study for the complete assignment of the 1H, 13C, and 15N NMR signals of ergometrine, methylergometrine, and their maleate salts. This information allowed for a better definition of their conformational equilibria. In addition, the stereochemistry and the intermolecular interactions in the solid state of the two maleate salts were deeply investigated by means of single-crystal X-ray diffraction, showing the capability of these derivatives to act as both hydrogen-bond donors and acceptors, and evidencing a correlation between the number of intermolecular interactions and their different solubility

(S)-Pramipexole and Its Enantiomer, Dexpramipexole : a New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates

A new chemoenzymatic method has been developed for the synthesis of (S)- and (R)-N-(6-hydroxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl) acetamide, two key synthons for the preparation of (S)-pramipexole, an anti-Parkinson drug, and its enantiomer dexpramipexole, which is currently under investigation for the treatment of eosinophil-associated disorders. These two building blocks have been obtained in good yields and high enantiomeric excess (30% and >98% ee for the R-enantiomer, and 31% and >99% ee for the S- one) through a careful optimization of the reaction conditions, starting from the corresponding racemic mixture and using two consecutive irreversible transesterifications, catalyzed by Candida antarctica lipase type A. Single crystal X-ray analysis has been carried out to unambiguously define the stereochemistry of the two enantiomers, and to explore in depth their three-dimensional features

A New Chemoenzymatic Synthesis of the Chiral Key Intermediate of the Antiepileptic Brivaracetam

Brivaracetam is a new anticonvulsant compound, recently approved as an antiepileptic drug. This drug substance presents a 4-substituted pyrrolidone structure: the (4R)-configuration of the stereocenter present on the heterocyclic ring is the main target of the synthesis. The described method allows to prepare the suitable optically pure 2-substituted primary alcohol by means of a Pseudomonas fluorescens lipase-catalyzed transesterification. The obtained (2R)-alcohol was easily transformed into the (3R)-3-propylbutyrolactone, an advanced intermediate of brivaracetam. The described synthetic pathway is completed with the chromatographic methods and the NMR analyses necessary to establish the chemical and the optical purity of the intermediates and of the final lactone

Layer- and bulk roton excitations of 4He in porous media

We examine the energetics of bulk and layer-roton excitations of 4He in various porous medial such as aerogel, Geltech, or Vycor, in order to find out what conclusions can be drawn from experiments on the energetics about the physisorption mechanism. The energy of the layer-roton minimum depends sensitively on the substrate strength, thus providing a mechanism for a direct measurement of this quantity. On the other hand, bulk-like roton excitations are largely independent of the interaction between the medium and the helium atoms, but the dependence of their energy on the degree of filling reflects the internal structure of the matrix and can reveal features of 4He at negative pressures. While bulk-like rotons are very similar to their true bulk counterparts, the layer modes are not in close relation to two-dimensional rotons and should be regarded as a third, completely independent kind of excitation

Experimental verification of the Heisenberg uncertainty principle for hot fullerene molecules

The Heisenberg uncertainty principle for material objects is an essential corner stone of quantum mechanics and clearly visualizes the wave nature of matter. Here we report a demonstration of the Heisenberg uncertainty principle for the most massive, complex and hottest single object so far, the fullerene molecule C70 at a temperature of 900 K. We find a good quantitative agreement with the theoretical expectation: dx * dp = h, where dx is the width of the restricting slit, dp is the momentum transfer required to deflect the fullerene to the first interference minimum and h is Planck's quantum of action.Comment: 4 pages, 4 figure

Nearest-neighbour distribution of distances in crystals from extended X-ray absorption fine structure

Extended X-ray absorption fine structure (EXAFS) is a powerful probe of the distribution of nearest-neighbour distances around selected atomic species. We consider here the effect of vibrational disorder in crystals. The potential of EXAFS for the accurate evaluation of the coefficient of bond thermal expansion and its temperature dependence is discussed, with the aim of stimulating and facilitating the comparison with the results from total scattering experiments. The meaning of the distribution asymmetry in crystals and its connection with the effective potential anharmonicity and the bond expansion is quantitatively explored by comparing the results for a number of different systems. The extent of the relative atomic vibrations perpendicular to the bond direction and the perpendicular to parallel anisotropy are correlated with the extent of lattice negative thermal expansion as well as with the ionic mobility in superionic crystals

Diffraction of complex molecules by structures made of light

We demonstrate that structures made of light can be used to coherently control the motion of complex molecules. In particular, we show diffraction of the fullerenes C60 and C70 at a thin grating based on a standing light wave. We prove experimentally that the principles of this effect, well known from atom optics, can be successfully extended to massive and large molecules which are internally in a thermodynamic mixed state and which do not exhibit narrow optical resonances. Our results will be important for the observation of quantum interference with even larger and more complex objects.Comment: 4 pages, 3 figure

Scattering length for helium atom-diatom collision

We present results on the scattering lengths of ^4He--^4He_2 and ^3He--^4He_2 collisions. We also study the consequence of varying the coupling constant of the atom-atom interaction.Comment: Contribution to Proceedings of the International Workshop ``Critical Stability of Few-Body Quantum Systems'' (Dresden, October 17--22, 2005