Improvement of some pharmaceutical properties of nocloprost by β- and γ-Cyclodextrin Complexation

Inclusion complexation of nocloprost, a potent antiulcer prostaglandin derivative, with -, -, and -cyclodextrins (CyDs) in aqueous solutions has been studied by the solubility method and¹³C-NMR spectroscopy. The steric requirement of host-guest interaction was reflected in the magnitude of the stability constants and the thermodynamic parameters of the inclusion complexes. Solid complexes of nocloprost with - and -CyDs in a molar ratio of 1 : 2 were obtained on the basis of aBs-type phase solubility diagram. The X-ray diffraction data suggested that nocloprost is included in the cylindrical channel formed by coaxial alignment of -CyD molecules to give a channel type structure. Release and thermal behavior of the solid complexes was examined and compared with nocloprost itself. The results indicated that the -CyD complex may have great utility among the three CyDs, being a rapid dissolving form of nocloprost with improved thermal stability.     

A novel synthesis of (+)-biotin from L-cysteine

(+)-Biotin (1) was synthesized in 25% overall yield over 11 steps from L-cysteine. The contiguous asymmetric centers at C-3a and C-6a were formed through a novel and highly stereoselective Lewis base-catalyzed cyanosilylation of alpha-amino aldehyde 3 to provide anti-O-TMS-cyanohydrin 4 with high stereoselectivity and in high yield (anti/syn = 92:8, 96%). Treatment of 4 with a di-Grignard reagent, 1,4-bis(bromomagnesio)butane, followed by carbon dioxide, efficiently installed the 4-carboxybutyl chain at C-4 to give keto acid 5. The final cyclization to bicyclic compound 7b, a precursor to 1, was realized by a palladium-catalyzed intramolecular allylic amination of cis-allylic carbonate 6b that was elaborated from 5.     

Rapid ruthenium-catalyzed synthesis of pyranopyrandiones by reconstructive carbonylation of cyclopropenones involving C[bond]C bond cleavage

Pyranopyrandiones were prepared by a novel ruthenium-catalyzed carbonylative dimerization of cyclopropenones via C-C bond cleavage. For example, treatment of dipropylcyclopropenone with a catalytic amount of Ru3(CO)12 and NEt3 in THF under 15 atm of carbon monoxide at 140 degrees C for 20 h gave a novel functional monomer, 3,4,7,8-tetrapropylpyrano[6,5-e]pyran-2,6-dione, in an isolated yield of 81%. Unsymmetrically substituted pyranopyrandiones were also obtained by ruthenium-catalyzed carbonylative coupling of cyclopropenones with alkynes under similar reaction conditions.     

Measurement of low concentrations of hydrogen in small samples by intermediate neutron moderation

An improved method based on the moderation of intermediate neutrons for the measurement of hydrogen in small samples is described. With the aid of boron and cadmium filters, a space shielded from slow neutrons is set up close to an isotopic neutron source shrouded by water moderator. A BF₃ proportional counter enclosed with a sample cell is placed in this space. The neutron count rate of the counter increases when a hydrogen-containing material is introduced into the cell, due to the moderation of intermediate neutrons passing through the filters. With a 1.3 μg²⁵²Cf neutron source, the lower limit of hydrogen detection for 200 ml samples in 10 min count time is 0.01 wt.%. This method is suitable for measuring the H₂O content of heavy water.     

Molecular Recognition Study on a Supramolecular System. Part 21. Inclusion Complexation Thermodynamics of Aliphatic Alcohols by Organoselenium Modified β-Cyclodextrins

The spectrophotometric titrations have beenperformed at 25–40 °C in aqueous solution to give the complexstability constants and the thermodynamic parametersfor the stoichiometric 1 : 1 inclusion complexation ofvarious aliphatic alcohols withmono[6-(phenylseleno)-6-deoxy]--cyclodextrin (2),mono[6-(o-, m-,p-tolylseleno)-6-deoxy]--cyclodextrin (3–5),mono[6-(p-chloro-phenyl-seleno)-6-deoxy]--cyclodextrin(6), mono[6-(benzylseleno)-6-deoxy]--cyclodextrin (7) and mono[6-(naphthaleneseleno)-6-deoxy]--cyclodextrin(8). On thebasis of the present and previous results, themolecular binding abilities and selectivities forguest aliphatic alcohols of the host -cyclodextrinderivatives (2–8) are discussed comparatively and globallyfrom the thermodynamic point of view. Thethermodynamic parameters obtained are criticalfunctions of the size/shape of aliphatic alcohols, andthe position and type of the substituent introduced tothe aromatic ring of -cyclodextrin's sidearm,which are elucidatedin terms of the conformational, electrostatic,hydrogen-bonding, and hydrophobic effects.     

THE CONFORMATIONAL ANALYSIS AND PHOTOISOMERIZATION OF RETINOCHROME ANALOGS WITH POLYENALS

Abstract— 3, 7-Dimethyl-2, 4, 6, 8, 10-dodecapentaenal was synthesized for reconstitution of the retinochrome analog. Its opsin shift was 1000 cm ¹ smaller than that of native retinochrome, whose chromophore contains the same number of double bonds. The conformational change from 6-s-trans to 6-s-cis , as figured in a retinal molecule, plays an important role in the formation of the retinochrome analog, based on the estimation of opsin shifts for retinal analogs locked in the 6-s conformation. Thus the conformation of the 6–7 single bond in the native retinochrome was suggested to be 6 -cis . Analysis of the circular dichroic spectra of retinochrome analogs revealed that the 6-s conformation is independent of the appearance of the β-band. The stereoselectivity in the photoisomerization of the retinal analogs by a retinochrome template depends on the hydrophobic binding in the region of the β-ionone ring.     

Electrical Properties of Polycrystalline Lithium Chloroboracite Prepared by the Sol-Gel Method

The electrical properties of polycrystalline lithium chloroboracite, Li4B7O12Cl, prepared by the sol-gel method were investigated in connection with their structure. Li4B7O12Cl pellets were prepared with different amounts of hydrochloric acid or ammonium chloride. The kind and amount of the chlorine source affected the formation of by-products (Li2B4O7, LiCl, a glass phase) and the morphology of the Li4B7O12Cl pellets. Thus their conductivity, which is dominated by grain boundary response owing to the high porosity of the materials, was also affected. The formation of Li2B4O7 as a by-product led to a higher activation energy and lower conductivity. In those pellets in which Li2B4O7 did form, an increase of the amount of glass phase led to higher conductivities.     

Ligand Substitution Reaction of Bis(ethylenediamine)glycinatocobalt(III) Complex with Ethylenediamine Catalyzed by the Photo-excited Tris(2,2′-bipyridine)ruthenium(II) Complex

Substitution reaction with ethylenediamine of coordinated glycinate ligand in bis(ethylenediamine)-glycinatocobalt(III) complex has been studied in the presence of photo-excited tris(2,2′-bipyridine)ruthenium(II) complex in alkaline aqueous solution (buffered around pH 12) containing 1.0M chloride ion at 25°C. VIS absorption and CD spectra were used for the racemate and the optically active isomers of the Co(III) complexes, respectively. The reaction was catalyzed by the excited Ru(II) complex to give tris(ethylenediamine)cobalt(III) complex. Mechanism of the ligand-substitution reaction and role of the excited Ru(II) complex were discussed.     

Deuterium relaxation time ofα-d-tryptophan included in cyclodextrin host molecules

Deuterium relaxation times ofd- andl--d-tryptophan included in -cyclodextrin derivatives were directly measured by deuterium NMR spectroscopy. The results showed that the molecular motion of the tryptophan molecule was strongly restricted even in the cavity of unmodified -cyclodextrin and the additional recognition groupings — ammonium and carboxylate — on -cyclodextrin did not affect the molecular motion of tryptophan, though the association constants were significantly enhanced.Deceased on March 22, 1987.