A novel carbon-carbon bond forming reaction has been developed by employing the rearrangement of sulfur ylides, easily derived by the preferential participation of carbene or carbenoid with the divalent sulfur, as a key step. This synthetic strategy has successfully been applied to the synthesis of physiologically active compounds.
Two new phenylpropanoid glycosides, named oleoacteoside and oleoechinacoside, have been isolated from the fresh leaves of Syringa reticulata (BLUME) HARA. These compounds were also detected in the methanolic extract of the leaves of Syringa vulgaris LINN. Their structures were elucidated on the basis of nuclear magnetic resonance, circular dichroism spectra and some other physicochemical evidence.
The rate of keto-enol tautomerization of p-substituted benzoylacetones in the absence of catalyst in 60% methanol at 20-30°C were followed spectrophotometrically. Absorption curves of keto and enol form were obtained by personal computer-treatment of the data taken (absorbance and wavelength), followed by preparation of calibration curves. Conversion percentage was obtained graphically. The rate for the reactions satisfied the reversible first-order kinetics : Rate=k1 (a-c-x)-k1 (c+x). Here, k1 and k-1 are the first-order rate constants of the ketonization and the enolization ; a, c and x are the concentration of the whole tautomer, of the keto form at the initial time and of consumed enol form at time t, respectively. In the activation parameters, enthalpies are nearly equal to the entropy terms in the ketonization, whereas each entropy term becomes a dominant factor in the enolization. A plot of log k1 (and/or log k-1) vs. log CH2O gave a straight line with a slope of ca. 3 in the ketonization (and/or enolization). From these findings, a probable mechanism which involves the hydrogen bonding annular complex by three molecules of water between enol hydrogen and methine carbon in the ketonization and/or methylene hydrogen and benzoyl oxygen in the enolization is postulated and discussed.
Synthesis and antibacterial activity of 7-[2-(2-aminothiazol-4-yl)-3-carboxy-2-propenoamido] cephalosporins and their derivatives are described. These compounds are of interest as carbon analogues of oximecephalosporins, 7-[2-(2-aminothiazol-4-yl)-2 (Z)-oxyiminoacetamido] cephalosporins having remarkable antibacterial activity. The synthesized 7-[2-(2-aminothiazol-4-yl)-3(Z)-carboxy-2-propenoamido]-cephalosporins (14, 19) show improved activity especially against the β-lactamase-producing strains. A 7-[2-(2-aminothiazol-4-yl) maleimido] cephalosporin (15) has been also prepared by cyclization of 7-[3-(2-aminothiazol-4-yl)-2-ethoxycarbonyl-2 (Z)-propenoamido] cephalosporin.
Cephalothin sodium (CET-Na) prepared according to the conventional freeze-drying methods is known to easily develop color during storage. Since amorphous CET-Na has been reported to be markedly unstable, the color development is thought to be due to the presence of traces of CET-Na in an amorphous state observed with scanning electron microscopy. Quantitation by use of the powder X-ray diffractometry of such traces of amorphous CET-Na has proved to be of little use. Thermogravimetry (TG) and differential scanning calorimetry (DSC) have demonstrated that the freeze-dried CET-Na by the conventional methods contains three types of CET-Na : amorphous (unstable phase), quasi-crystalline (metastable phase). Pyrolysis initiation temperatures of these three types of CET-Na have been demonstrated to become higher in this order. A new parameter for the evaluation of non-crystallinity of CET-Na has been introduced, in which the ratio is calculated from the data of the total weight loss observed through the pyrolysis of both amorphous and quasi-crystalline CET-Na against the total weight loss of all components during the pyrolysis of sample specimen. The ratio thus calculated is defined as "non-crystallinity". This new parameter has successfully been introduced to establish a good correlation to the degree of increasing color intensity with aging of freeze-dried CET-Na.
Cephalothine sodium (CET-Na) in crystals can be obtained by freezing the aqueous solution and subsequent warming at a fixed temperature for facilitating crystallization prior to vacuum application for drying. The product has, however, been found to unavoidably contain traces of the amorphous CET-Na, which causes a rapid color development during storage. By using thermal analysis, differential scanning calorimetry (DSC), electric conductometry, and polarized light cryomicrographic techniques, the solubilities in water, freezing point, eutectic point, and melting behavior of CET-Na in aqueous solution were investigated. The investigation demonstrated that CET-Na in supersaturated aqueous solution is very stable, and that seeding with microcrystalline CET-Na to the supersaturated solution and subsequent cooling of the mixture till its freezing point gives neither any evidence for crystallization nor for growth of the seed crystals. The freeze-drying of CET-Na in the supersaturated solution after seeding has been demonstrated to give crystalline CET-Na contaning neither of amorphous nor of quasicrystalline form.
The present study was carried out to elucidate a centrally acting muscle relaxant effect of chloroform soluble fraction and its component, namely, ligustilide, cnidilide and senkyunolide obtained from the rhizome of Cnidium officinale MAKINO. These three compounds were isolated from the chloroform soluble fraction by column chromatography on silica gei. The centrally acting muscle relaxant effect was investigated on the crossed extensor reflex in anesthetized rats and these samples were suspended in 0.5% carboxymethyl cellulose solution and administered i.p. These three compounds as well as the chloroform soluble fraction depressed the reflex response. The depressive potencies among them were almost the same and their potencies were also the same or somewhat weaker as that of mephenesin. As a curare-like action was not observed, a muscle relaxation induced by these phthalide compounds is considered to be due to central origin.
Experiments by in vitro screening test were made concerning many kinds of crude drugs, to determine anti-tumor activity in tissue cultured cell lines, such as human cancer cell (JTC-26) and a human normal embryonic cell (HE-1) lines. Consequently a group with high selective toxicity, in which the crude extracts of some traditional drugs inhibited the growth of the cancer cells in 500-120 μg/ml, but not normal cells, was shown.
In the general rule, Puerariae Flos or it's combination drugs are used in traditional medicinal system for counteraction to drinking among Japanese and Chinese therapy. One of such drugs is Kakkakaiseito. Here we report the results of investigation on some pharmacological actions including alcoholic metabolism. The experiments were carried out to confirm its actual effect on alcohol, acetaldehyde and ketone body metabolism in the blood and the alteration of behaviour pattern of mice. Drugs used in this study were methanolic extract (PF-ME), isoflavonoid fraction (PF-IF) and triterpenoid saponin fraction (PF-SP) isolated from Puerariae Flos. Each drug was orally administrated to mice. These results were shown as follows : the concentrations of blood alcohol and acetaldehyde decreased more after the treatment with PF-IF (800 mg/kg) than those of the control group. This fact was evidenced remarkable effects with area under the blood concentration-time curve, mean residence time, and variance residence time and values on the moment analysis. However, a reduction effect was not recognized by the treatment with PF-SP (1000 mg/kg). Moreover, PF-ME and PF-IF suppressed the increment of spontaneous movement induced by alcohol administration, whereas PF-SP did not prevent the decrease in the increment caused by alcohol administration. These results support the basis that Puerariae Flos or its combination drugs is used in a traditional medicinal system for counteraction to drinking. However, further investigation is necessary.
The orally co-administered sodium bicarbonate significantly enhanced the blood concentration of sulfadimethoxine at the early stage after oral administration to rabbits, by increasing its intestinal absorption. On the other hand, the sodium bicarbonate significantly reduced the blood concentration of sulfisoxazole at the elimination phase after oral administration to rabbits, by increasing its urinary excretion. The fact that sodium bicarbonate exhibits different effects in the disposition of these two sulfonamides is an interesting example to gain a better understanding for the complexity of drug interaction.