Review the recent progress of X-ray analysis and summarize some topics of structural studies by X-ray analysis. Describe the trends in data accumulation and dissemination using information network systems, which make us possible to develop advanced methods of utilization of structural informations. Future prospects have also been described.
A new chalcone methyl ether, named sappanchalcone (I), C16H14O5, mp 199.5-200.5°C was isolated from the heartwood of Caesalpima sappan L. (Sappan Lignum). On the basis of the spectrometric data and the synthesis from 2-O-methylresacetophenone (=isopaeonol) and protochatechualdehyde, the chemical structure of I was established as 2'-methoxy-3, 4, 4'-trihydroxychalcone (=2'-O-methylbutein). It has been proposed that brazilin, a distinguished constituent of this heartwood, is biosynthesized via a homoisoflavone intermediate from a hypothetic chalcone methyl ether, to which sappanchalcone (I) just corresponds.
Four dammarane-oligoglycosides named gypenosides XXXVI (1), XXXVII (2), LIII (3) and LIV (4) were isolated from the aerial parts of Gynostemma pentaphyllum MAKINO collected in Hyogo pref. On the basis of chemical and physicochemical evidence, they were characterized as follows : 1, 19-oxo-3β, 20 (S)-dihydroxydammar-24-ene-3-O-[β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside]-20-O-β-rutinoside : 2, 19-oxo-3β, 20 (S)-dihydroxydammar-24-ene-3-O-[β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside]-20-O-β-primeveroside : 3, 19-oxo-3β, 12β, 20 (R)-trihydroxydammar-24-ene-3-O[β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside] : 4, 3β, 12β, 19, 20 (S)-tetrahydroxydammar-24-ene-3-O-[β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside].
Two new erythrinan alkaloids, named erythlaurine and erythramide, and the known alkaloids stepholidine (XII) and O-methylflavinantine (XIII) were isolated from the leaves of Cocculus laurifolius. On the basis of chemical and spectroscopic evidence, the structures of erythlaurine and erythramide were determined as VII and X, respectively.
From the basic fraction of the ethereal extract of Ginseng Radix (Panax ginseng C.A. MEYER, Araliaceae), five methoxypyrazine and eight alkylpyrazine derivatives were identified by gas chromatography and gas chromatography mass spectrometry. The methoxypyrazine derivatives were likely to be of major significance in the characteristic earthy, green aroma with moldy undertone of Ginseng Radix. One of them was a novel methoxypyrazine derivative, 3-sec-butyl-2-methoxy-5-methylpyrazine (6), and the structures of 3-isopropyl-2-methoxy-5-methylpyrazine (3) and 3-sec-butyl-2-methoxy-5-methylpyrazine (6) were estimated from mass spectra of known methoxypyrazine derivatives, 2-isopropyl-3-methoxypyrazine (1) and 2-sec-butyl-3-methoxypyrazine (4), and confirmed by their syntheses. 3-sec-Butyl-2-methoxy-5-methylpyrazine (6) was found to possess a characteristic floral, moldy, green aroma with an odor threshold of 2.0 parts per 109 parts of water. The mass spectra of methoxypyrazine derivatives showed similar systematic fragmentations starting from McLafferty rearrangement and γ-cleavage, and the mass spectrometry was found to be a usefull method for structural elucidation and detection of methoxypyrazine derivatives.
The effects of decoctions of four Kanpo-prescriptions (Keishi-Ni-Eppi-Ittoh-Ka-Ryoh-Jutsu-Bu, Keishi-Ka-Jutsu-Bu-Toh, Keishi-Shakuyaku-Tchimo-Toh, and Yokuinin-Toh), which are widely used in Japan for the therapy of rheumatoid arthritis, on macrophage procoagulant activity was investigated. Peritoneal exudate cell of guinea pig was used as a macrophage source. These four decoctions were added to the macrophage suspensions in vitro, and each suspension was incubated for 14 h at 37°C. Macrophage procoagulant activity was measured by the method similar to that of determination of the recalcification time of the plasma. It was found that the decoctions of these four Kanpoprescriptions potentiated remarkably the macrophage procoagulant activity. In addition, we examined similarly the effect on the macrophage procoagulant activity of 18 kinds of crude drug including the constituents of these four prescriptions, and the decoctions of three kinds of crude drug, Byakujutsu, Sohjutsu, and Maoh, had apparent enhancing effect on it. Since every four Kanpo-prescription described above includes Byakujutsu or Maoh, their potentiating activity on macrophage procoagulant activity was dependent on the active substances of Byakujutsu and Maoh.
Changes in the electrical conductivity (conductivity) of various drugs in aqueous frozen phase were measured at increasing temperature and logarithm of the conductivity was plotted against reciprocal of absolute temperature. The change in the conductivity after the frozen solution being led to its eutectic state by either annealing or seeding was examined to obtain eutectic temperature. Investigation disclosed the relationship between collapse temperature (cp) observed during freeze-drying and the change in the conductivity observed in the process of amorphous freezing. Ascorbic acid, xylose, etc., when subjected to amorphous freezing, were found to show a bend, while cephalothin sodium, cephamandol sodium, etc. exhibited a sharp increase in the conductivity at individual cp. When the curve shows a bend, cp varies with the concentration of drug : this dependence of cp upon concentration was not observed in cases when a sharp increase in the conductivity can be observed. The sharp increase in the conductivity can be correlated with an endothermic peak or DSC. Generation of a sharp increase in the conductivity is interpreted to indicate glass transition accompanied with heat absorption in amorphous-frozen state of an aqueous drug solution.
Investigation has been made to obtain the crystallinity of cephalothin sodium in seeded and frozen aqueous solution from electrical conductivity (conductivity), with a result that crystallinity (αt) can be given by the equation of αt=λT-λt/λT, where λT is the initial conductivity and λt stands for the conductivity obtained after t hours. Observed values of crystallinity by the conductivity method are in good agreement with crystallinity data by infrared method and X-ray diffraction method of the freeze-dried material. Further investigation has been made to find out whether it is possible to apply the no-seeding conductivity method for the crystallinity of dicethiamin hydrochloride in solution capable of spontaneous nucleation and transformation to its crystalline state. The result has consequently demonstrated that, in some cases of no-seeding, the phase transition is not uniform, or otherwise, the conductivity change provides an incomplete indication of nucleation and growth of perfect crystals. From the above, it may as well be said to be safe to set a limit to a seeded system, when the authors' conductivity method is applied for obtaining the crystallinity of a drug in frozen solution.
The electrical conductivity (conductivity) of cephalothin sodium (KF) in the aqueous frozen phase was measured at increasing temperature with varying concentrations. Above concentration of 5.0%, a sharp increase in the conductivity was found at -18--22°C. This phenomenon occurred during rewarming after recooling from -5°C to -50°C. On the other hand, below concentration of 1.5%, the conductivity fell after a rise with increasing temperature. This change of conductivity did not occur during rewarming. A sharp increase in the conductivity was found to correspond to the small endothermic peak of DSC. The concentration dependence of pH of KF in the aqueous solution was measured to demonstrate micelle formation. It may be attributed to the micelle formation that changes of the conductivity of KF in the aqueous frozen phase depend on the concentration of KF. The heat of solution of a drug easily capable of spontaneous nucleation and crystallization in the aqueous frozen phase was compared with that of a drug hardly capable of such a transformation : it was found out that a drug having a low heat of solution hardly transform to crystal owing to spontaneous nucleation. The difficulty of spontaneous transformation to crystal of KF in the aueous frozen phase will certainly be due to its low heat of solution, and the absence of hydrated crystals in spite of the micelle formation.
The lamellar liquid crystalline phase (D2 phase) and a particle appearing in a region of a surfactant-cetostearyl alcohol-water ternary system, and the particle of the emulsion which was made by substituting part of the cetostearyl alcohol for a liquid paraffin were observed using a cryo scanning microscope. The D2 phase gave an image of overlapped lamellae. The particle of ternary system consisted of spherically overlapped lamellae. The oil droplet in the emulsion was surrounded by the spherical lamellae, as if it were protected by the spherical lamellae. Thus the internal structure of the emulsion stabilized with cetostearyl alcohol can be described as follows. The particles consist of oil droplets and spherical lamellae which surround them. The outer phase is a dispersion of the D2 phase platelets in an aqueous phase to form a gel. The layer of the spherical lamellae becomes thin with decreasing cetostearyl alcohol content.
Anti-inflammatory drug pirprofen (PF) is an amphoteric which contains a nitrogen atom and a carboxyric acid group. PF is practically insoluble in water and not stable enough (against moisture, temperature, light) for a certain dosage form, having an irritant sensation on the throat mucosa. These undesirable properties of PF were found to be improved effectively by forming an inclusion complex with β-cyclodextrin (β-CyD). The molar ratio of PF-β-CyD complex was 1 : 1 in dilute aqueous solution, while 2 : 3 in solid state. The stability constant of complex changed with pH value, and it gave a maximum value at pH 7.5. The different inclusion mode of complex in acidic and alkaline solutions was proposed by means of various spectroscopies. The increase in dissolution rate of PF by β-CyD complexation was rather small in acidic medium, because of the dissociation of complex. The bioavailability of inclusion complex was compared with that of PF alone after oral administration to dogs and it was found that the plasma level of PF was almost equal in both cases.
Powdered whole bodies, internal organs, flesh and shell of soft-shelled turtles (Trionyx sinensis WIEGMANN) were extracted with 60% ethanol, and fractionated by gel filtration. By pharmacologically sequential bioassay on the isometric tension in isolated mouse mesenteric veins, we obtained three types of fractions which showed (1) a contraction by itself, (2) a potentiation of and (3) an inhibition of noradrenaline (NA)-induced contractions. The third fraction was further fractionated by ion exchange chromatography into two components which inhibited the NA-induced contraction in a non-competitive mode or in a mixed type of competitive and non-competitive modes.
3-Arylmethylene-5, 5-dimethyltetramic acids (5a-i) were synthesized from 5, 5-dimethyltetramic acid (3) and aromatic aldehydes by an acid catalyzed aldol condensation. 10-Aryl-3, 3-dimethyl-2, 3, 4, 10-tetrahydro-1H-pyrrolo [3, 4-c] [1, 5] benzothiazepin-1-ones (9a-g) were prepared by Michael reaction between 2-aminobenzenethiol and 3-arylmethylene-5, 5-dimethyltetramic acids in good yield.