Formation of Supramolecular Polymers Constructed by Cyclodextrins with Cinnamamide

-Cyclodextrin having cinnamamide at 6- or 3-positions (6-CiNH--CD, 3-CiNH--CD) and -cyclodextrin with cinnamamide on 6-position (6-CiNH--CD) have been prepared. Supramolecular structures were formed in the solid state or aqueous solutions and characterized by measurements of NMR and vapor pressure osmometry (VPO). The results indicate that 6-CiNH--CD formed insoluble supramolecular polymers in the solid state, while 6-CiNH--CD and 3-CiNH--CD formed supramolecular complexes in aqueous solutions. 6-CiNH--CD was found to form a dimer in an aqueous solution. 3-CiNH--CD formed intermolecular complexes to give supramolecular polymers. The differences of the position of guest part on cyclodextrins caused to give a variety of supramolecular structures in aqueous solutions.     

Simultaneous determination of sulfamethoxazole and trimethoprim in human plasma by capillary zone electrophoresis

A capillary electrophoretic method for the simultaneous determination of sulfamethoxazole and trimethoprim in plasma was developed. Sulfamethoxazole and trimethoprim extracted from human plasma with ethyl acetate were analyzed at 20 kV and 25 degrees C using 15 mm phosphate buffer (pH 6.2) as the electrolyte. The detection was by UV at 220 nm. The run time was 8.0 min and the limit of quantification was 10.00 microg/mL for sulfamethoxazole and 2.00 microg/mL for trimethoprim. The recovery was >99% for both compounds. This method enabled the detection of sulfamethoxazole and trimethoprim in plasma of patients after oral ingestion of their combined formulation. The present simple and rapid method is applicable to drug monitoring in immunocompromised patients who are taking the combined formulation of these compounds for the treatment or prophylaxis of Pneumocystis carinii pneumonia.     

Dimethylsilyl ketene acetal as a nucleophile in asymmetric Michael reaction: enhanced enantioselectivity in oxazaborolidinone-catalyzed reaction

[reaction: see text] Dimethylsilanyl [Me2Si(H)] ketene S,O-acetal 6b is an effective nucleophile that retards the undesirable Si+-catalyzed racemic pathway in the oxazaborolidinone-catalyzed asymmetric Michael reaction. Through the further suppression of the Si+-catalyzed pathway by carrying out the reaction in the presence of 2,6-diisopropylphenol and t-BuOMe as additives, enantioselectivity up to 98% ee could be achieved for a variety of acyclic enones.     

Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex

Full details of our direct Michael addition of unmodified ketones using new asymmetric zinc catalysis are described. Et(2)Zn/(S,S)-linked-BINOL complexes were successfully applied to direct 1,4-addition reactions of hydroxyketones. The first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was effective for 1,4-addition of 2-hydroxy-2'-methoxyacetophenone (3). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we found that a 1,4-addition reaction of beta-unsubstituted enone proceeded smoothly at 4 degrees C to afford products in high yield (up to 90%) and enantiomeric excess (up to 95%). In the case of beta-substituted enones, however, the first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was not at all effective. The second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with MS 3A system was developed and was effective for various beta-substituted enones to afford products in good dr, yield (up to 99%), and high enantiomeric excess (up to 99% ee). With the Et(2)Zn/1 = 4/1 systems, catalyst loading for beta-unsubstituted enone was reduced to as little as 0.01 mol % (substrate/chiral ligand = 10 000). The new system was also effective for 1,4-addition reactions of 2-hydroxy-2'-methoxypropiophenone (9) to afford chiral tert-alcohol in high enantiomeric excess (up to 96% ee). Mechanistic investigations as well as transformations of the Michael adducts into synthetically versatile intermediates are also described.     

X-ray diffraction analysis of nonequilibrium states in crystals: observation of an unstable conformer in flash-cooled crystals

Some molecules with a molecular skeleton similar to that of stilbenes and azobenzenes show orientational disorder in the crystals. If the disorder is dynamic, a conformational interconversion takes place through a pedal motion. In this study X-ray diffraction analyses of (E)-stilbene (1) and azobenzene (2) were carried out at various temperatures. We succeeded in observing thermodynamic nonequilibrium states that were generated by fast freezing of the conformational interconversion at low temperatures. The populations of the two conformers in crystals of 1 at 90 K varied with the cooling rate. Flash cooling of a crystal of 2 from room temperature to 90 K made it possible to observe the minor unstable conformer that does not exist in the equilibrium state at the same temperature.