Chiral separation of the four stereoisomers of a novel antianginal agent using a dual cyclodextrin system in capillary electrophoresis

Reported here is an analytical method enabling the stereochemical resolution of a new antianginal compound possessing two stereogenic centers, leading to four stereoisomers. Only one of these isomers is currently under development as a novel antianginal agent and consequently, the other three isomers are considered as unwanted chiral impurities. Therefore, an enantioselective method is required in order to check its enantiomeric purity. This paper presents a method exploiting the high efficiency of capillary electrophoresis and the complexing properties of cyclodextrins to achieve the separation of the four stereoisomers of this weakly basic compound (pKa = 7.4). For this purpose, the combination of a neutral cyclodextrin, hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), and an anionic cyclodextrin, carboxymethyl-beta-cyclodextrin (CM-beta-CD), was added to the separation buffer running in an uncoated silica capillary. After selection of the suitable cyclodextrin system, satisfactorily separation conditions were as follows: 30 mM phosphate buffer (pH 6.4) containing 10 mM of HP-gamma-CD and 10 mM of CM-beta-CD, running voltage +30 kV. The resulting run time and resolutions were respectively about 17 min and between 1.95 and 2.84. Linearity curves (0.993 < r2 < 0.998) are also shown.     

Comparison of dephasing times for vibrational and rotational coherent anti-Stokes Raman scattering: implications for velocimetry

Time-domain coherent anti-Stokes Raman scattering experiments have been carried out by probing vibrational and pure rotational lines of nitrogen in the Doppler broadened regime. The theoretical analysis of the transient responses outlines the role of the geometrical effects. For pure rotational CARS, it is shown that the main contribution to the dephasing of the Raman coherence results from the change in direction between the pump and anti-Stokes wave vectors whereas the difference between the modulus of these two wave vectors accounts for dephasing in vibrational CARS. Furthermore, we demonstrate that the range of operation of time-domain CARS velocimetry is extended by probing pure rotational lines. The predictions are validated by experiments which are performed both in a static gas cell and in a Mach 10 supersonic flow. Received: 30 March 2000 / Revised version: 9 June 2000 / Published online: 13 September 2000     

Temporal behavior of a high repetition rate infrared optical parametric oscillator based on periodically poled materials

The temporal behavior of a nanosecond pulsed singly resonant periodically poled lithium niobate optical parametric oscillator has been studied both theoretically and experimentally. Taking into account the cylindrical symmetry of the system, a numerical model based on the Hankel transform has been developed. Good agreement is obtained between experiment and simulation. Moreover, the computation time is reduced roughly by a factor of 60 compared to the usual simulation software. Received: 23 April 2001 / Published online: 19 September 2001     

Conformational analysis and crystal structure of {[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt

{[1-(3-Chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt (C(20)H(22)ClF(2)N(3)O, C(4)H(4)O(4)) (1) was synthesized and characterized by the complete (1)H, (13)C and (19)F NMR analyses. The conformation of the piperidin ring, in the solution state, was particularly studied from the coupling constants determined by recording a double-quantum filtered COSY experiment in phase-sensitive mode. (1)H NMR line-shape analysis was used, at temperatures varying between -5 and +60 degrees C, to determine the enthalpy of activation of the rotational barrier around the CN bond. Compound 1 crystallizes in the triclinic space group P1 with a=8.517(3) Angstrom, b=12.384(2) Angstrom, c=12.472(3) Angstrom, alpha=70.88(2) degrees, beta=82.04(2) degrees, gamma=83.58(2) degrees. The results strongly indicate that the solid and solution conformations are similar. Thermal stability and phases transitions were investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore polymorphism screening was studied from recrystallization of 1 performed in seven solvents and by slurry conversion in water. The X-ray powder diffraction (XRPD) and differential scanning calorimetry results suggested that 1 crystallizes into one crystalline form which melts at 157 degrees C (DeltaH=132 J g(-1)).