Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models

Glycyrrhetinic acid (Ia) and eighteen related derivatives were examined for antiulcer activity using stress-induced gastric lesions (restraint plus water immersion at 25 degrees C) in mice and rats as screening tests. Among the compounds tested, dihemiphthalate derivatives of 18 alpha- or 18 beta-olean-12-ene-3 beta,30-diol (IV, IIId), 18 beta-olean-9(11)12-diene-3 beta,30-diol (VIc), and olean-11,13(18)-diene-3 beta,30-diol (VIIc) showed potent inhibition of gastric lesion formation at a dose of 12 or 25 mg/kg (p.o.); carbenoxolone sodium (Ib) significantly suppressed the lesion formation at a dose of 500 mg/kg (p.o.). Further evaluation of the antiulcer activity was carried out mainly for compound IIId. Compound IIId (p.o.) prevented the formation of indomethacin-induced or 0.6 N HCl-induced gastric lesions; the latter antiulcer effect was noted even in the combined treatment with indomethacin, suggesting that the effect occurs independently of endogenous prostaglandins. In contrast, compound IIId had no preventive effect against Shay rat ulcer when intragastrically (i.g.) administered; further, no antisecretory effect was seen by i.g. application in pylorus-ligated rats. Administration of compound IIId for 2 weeks accelerated the healing rate of acetic acid-induced gastric ulcer in rats. No significant change in urine excretion was observed after its consecutive administration for 3 d. These results suggest that dihemiphthalate derivatives (IIId, IV, VIc, VIIc) may produce a strong antiulcer activity, probably by strengthening some gastric mucosal defensive mechanism.     

Anti-plasmin inhibitor. VI. Structure of phlorofucofuroeckol A, a novel phlorotannin with both dibenzo-1,4-dioxin and dibenzofuran elements, from Ecklonia kurome Okamura

Phlorofucofuroeckol A (1), a novel phlorotannin with both dibenzo-1,4-dioxin and dibenzofuran elements, has been isolated from the brown alga Ecklonia kurome OKAMURA as a potent anti-plasmin inhibitor. Its structure has been elucidated to be 1,11-di(3,5-dihydroxyphenoxy)- benzofuro[3,2-a]dibenzo[b,e][1,4]dioxin-2,4,8,10,14-pentaol on the basis of the spectral data, in particular, by means of negative nuclear Overhauser effect (NOE) and long-range carbon-proton couplings (2JCH and 3JCH). Phlorofucofuroeckol A inhibited the action of alpha 2-macroglobulin (IC50 = 1.0 micrograms/ml) and alpha 2-plasmin inhibitor (IC50 = 0.3 micrograms/ml), the main plasmin inhibitors in plasma.     

Recognition of phosphate monoester dianion by an alkoxide-bridged dinuclear zinc(II) complex

Recognition of phosphate monoester dianion by an alkoxide-bridged dinuclear zinc(II) complex (Zn2L3+) has been studied (L = alkoxide species of 1,3-bis[bis(pyridin-2-ylmethyl)amino]propan-2-ol). Potentiometric pH titration study disclosed a 1 : 1 phenyl phosphate complexation with Zn2L3+ in aqueous solution. The dissociation constant (= [Zn2L3+][PhOPO3(2-)]/[Zn2L3+-PhOPO3(2-)]) is an extremely small value of 2.5 x 10(-8) mol dm(-3) at 25 degrees C with I = 0.10 (NaNO3). The X-ray crystal analysis of the dizinc(II) complex with p-nitrophenyl phosphate showed that the phosphate dianion binds as a bridging ligand to the two zinc(II) ions.     

Fabrication of convex-shaped polybenzylsilsesquioxane micropatterns by the electrophoretic sol–gel deposition process using indium tin oxide substrates with a hydrophobic-hydrophilic-patterned surface

Polybenzylsilsesquioxane (BnSiO_3/2) particles become a supercooled liquid through a heat treatment above the glass transition temperature (T _g) of the particles. Micropatterns of BnSiO_3/2 thick films with high transparency were obtained by the electrophoretic deposition of the BnSiO_3/2 particles on indium tin oxide (ITO)-coated substrates with a hydrophobic-hydrophilic-patterned surface and subsequent heating above T _g of the particles. It was found that the control of electrophoretic deposition conditions, in which the amounts of the particles deposited on the substrates were changed, led to two types of micropatterning processes of the BnSiO_3/2 thick films. In the first process, the particles were selectively deposited on the hydrophilic areas after the electrophoretic deposition. In the second process, the particles were deposited on the whole area of the ITO-coated substrate with hydrophobic-hydrophilic patterns after the electrophoretic deposition. Due to the difference in wettability of BnSiO_3/2 molten liquids between hydrophobic and hydrophilic surfaces, the molten liquids on the hydrophobic areas, which were obtained by heating above T _g of the particles, migrated toward the hydrophilic areas. In both the processes, convex-shaped BnSiO_3/2 micropatterns with high transparency were fabricated only on the hydrophilic areas after a heat treatment above T _g of the particles.     

Catalytic asymmetric synthesis of 1,1'-spirobi[indan-3,3'-dione] via a double intramolecular C-H insertion process

A highly efficient one-pot construction of optically active 1,1'-spirobi[indan-3,3'-dione] derivative (up to 80% ee) has been achieved by exploiting the double intramolecular C-H insertion reaction of dimethyl 2,2'-methylenebis(alpha-diazo-beta-oxobenzenepropanoate) under the influence of dirhodium(II) tetrakis[N-phthaloyl-(R or S)-tert-leucinate] as a catalyst.