Molecular orbital studies on the binding forces of CH₃CN-BH₃, HCN-BH₃, CH₃NC-BH₃ and HNC-BH₃ complexes were carried out in comparison with other borane compounds. For the CH₃CN-BH₃ and HCN-BH₃ complexes, the electrostatic energy contributes dominantly, while the charge transfer energy and polarization energy are also significant. For the CH₃NC-BH₃ and HNC-BH₃ complexes, on the other hand, the polarization energy, the charge transfer energy and the electrostatic energy contribute comparably. The bonding of BH₃ with nitriles and isonitriles is end-on rather than side-on, since electrostatic interaction is most favored when the electron-deficient B of BH₃ with nitriles and isonitriles is end-on rather than side-on, since electrostatic interaction is most favored when the electron-deficient B of BH₃ approaches the N (or C) end of RCN (or RNC) along an extension of the CN (or NC) axis.

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The platinum complexes of diaminocarboxylates (charged complexes) and their ethyl ester derivatives (non-charged complexes) were prepared and examined for antitumor activity. The non-charged complexes are antitumor-active, while the charged complexes are inactive. The interaction of deoxyribonucleic acid (DNA) with the charged and non-charged complexes was examined by means of ultraviolet (UV) difference spectroscopy. Since the UV difference spectral patterns obtained in this work were almost the same, the binding mode of the charged complexes to DNA seems to be the same as that of the non-charged complexes. However, the presence of negative charge lowers the reactivity of the platinum complexes with DNA. The antitumor-inactivity of the charged complexes may be due to a combination of their reduced ability to permeate into cells and the lower reactivity with DNA.

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The function of the hydrogen bond between His 57 and Asp 102 in serine proteases was studied by ab initio molecular orbital calculations on a model of the enzyme. The calculated hydrogen bond distance was 2.73Å, which is in good agreement with the distances obtained by X-ray diffraction analyses of trypsin. The stabilization energy is -30.0 kcal/mol. The electrostatic interaction term is the dominant contributor. The polarization energy and the charge transfer energy are also significant. The charge transfer energy is largely due to charge transfer from the aspartic acid to the histidine. The lone pair molecular orbital (LPMO) level of the nitrogen of His 57 increases substantially due to the electrostatic interaction between the two molecules. As a result, the charge transfer interaction between Ser 195 and the LPMO increases, and the increase of LPMO level should play a role in lowering the barrier height of proton transfer from Ser 195 to His 57 in trypsin. The populations of the LPMO upon complex formation are changed due to the polarization term. The populations of the outer shell of the nitrogen LPMO increase substantially, and hence the stabilization energy between His 57 and Ser 195 will increase with complex formation between His 57 and Asp 102. On the basis of optimized calculations of the complex, it is suggested that the hydrogen-bond structure in trypsin involves the anion of Asp 102, the neutral form of His 57 and the neutral form of Ser 195.

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The transfer of three commercial diuretics (furosemide, bumetanide and hydroflumethiazide) in the biophase was investigated using rabbits. Pharmacokinetic analysis based on the two-compartment open model was performed. The biological half-lives calculated from the β phase of rabbit plasma level time courses were almost the same and were extremely short (20-40 min), in spite of the large differences among the three diuretics in plasma protein binding. The results of renal clearance experiments using rabbits indicated a large contribution of tubular secretion (approximately 80-90%). Therefore, it is suggested that the plasma protein is involved in the transport of diuretics to the kidney.

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3-Formylrifamycin SV (4) was found to react with formalin in combination with primary alkylamines to give 2, 3-dihydropyrimido [4, 5-b] rifamycin derivatives 3. The iminium carbon of 3 was found to be reduced when primary alkylamines with at least one hydrogen atom at the α-position were used. The addition of an alcoholic OH group to the iminium carbon of 3 is also described.

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The effect of histidylhistidine on the copper (II)-catalyzed oxidation of ascorbic acid was investigated kinetically by the polarographic technique. At pH 3.8 histidylhistidine had an accelerating effect on the copper (II)-catalyzed oxidation. In contrast, at pH above 5.0 it exerted an inhibitory effect. The visible and CD spectra of the copper (II)-histidylhistidine system obtained at pH 3.8 and 5.9 indicate that different types of complex species are present predominantly at each pH. That is, at the former pH copper (II) is linked by a coordinate bond to the N-groups of the two imidazole rings in histidylhistidine, while at the latter pH two other N-groups take part in further bond formation. It appears that lability of two of the four coordinate bonds in the copper (II)-histidylhistidine complexes with respect to ligand substitution is a prerequisite for catalytic activity. The effects of histidine, imidazole and acetylhistidine on the copper (II)-catalyzed oxidation of ascorbic acid were compared. The results suggest that the accelerating effect of histidylhistidine arises from the two imidazole rings in the molecule.

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The ring transformation reaction of nonfluorescent 4-amino-1H-1, 5-benzodiazepine-3-carbonitrile hydrochloride (1) with hydrogen peroxide to fluorescent benzimidazole was applied for the determination of hydrogen peroxide by fluorometry. Peroxidase was employed as a catalyst in the reaction. The measurable range was from 5.880×10^-7 mol/l to 1.176×10^-5 mol/l of hydrogen peroxide. Although the detection limit is not as good as that with diacetyldichlorofluorescin (detection limit of about 10^-8 mol/l), 1 has the advantages of better solubility in water and stability against oxidation by air.

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The two isomers of 5-aminomethyltetrahydro-2H-pyran-2-carboxylic acid (9) and those of 5-aminomethyl-1, 4-dioxane-2-carboxylic acid (18) were synthesized from 2-ethoxycarbonyl-3, 4-dihydro-2H-pyran-5-carboxylic acid chloride (2) and dimethyl 1, 4-dioxane-2, 5-dicarboxylate (15), respectively. From the aminoacetal (19) and dimethyl bis (hydroxymethyl) malonate (21), trans-2-aminomethyl-1, 3-dioxane-5-carboxylic acid (26A) was synthesized. The configurations of these isomers were determined on the basis of their nuclear magnetic resonance spectra, and the preferred conformations of the isomers in aqueous solution were similarly deduced. No compound showed antiplasmin activity more potent than that of trans-4-aminomethylcyclohexanecarboxylic acid (1A).

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Four isomers of 4-aminomethyl-1, 2-cyclohexanedicarboxylic acid (4) were synthesized from dimethyl 4-cyanophthalate (2) via 4-aminomethylphthalic acid (3), and the isomers of 4-aminomethyl-2-carboxymethylcyclohexanecarboxylic acid (14) were also synthesized from 5-aminophthalide (10). The configurations and preferred conformations in aqueous solution of the former isomers were determined on the basis of the nuclear magnetic resonance spectra and by converting the compounds to trimethyl 1, 2, 4-cyclohexanetricarboxylates (5), which were compared with 5 obtained from methyl bicyclo [2. 2. 2]-5-octene-2-carboxylate (8), trimethyl trimellitate (6), and trimellitic acid (9). Those of the latter isomers were deduced from the nuclear magnetic resonance spectra snd the relationships of the isomerization products of 14. The compound t-4-aminomethyl-r-1, c-2-cyclohexanedicarboxylic acid (4C), which is thought to exist in the 1-e, 2-a, 4-e form in aqueous solution, showed more potent antiplasmin activity than trans-4-aminomethyl-cyclohexanecarboxylic acid (1A).

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Nuclear magnetic resonance spectroscopy with a lanthanide chemical shift reagent was applied for the structural determination of cis-and trans-isomers of 3-alkenoic acids, prepared as substrates for some enzyme reactions related to fatty acid metabolism. The configuration of N-acetylcysteamine derivatives of cis-2-alkenoic acids was also determined by the same technique.

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Cumene hydroperoxide (CHP)-and ethyl hydroperoxide (EHP)-supported oxidations of aminopyrine catalyzed by catalase were investigated by electron spin resonance (ESR) studies. The oxidations were also monitored through the measurement of formaldehyde. The EHP-supported oxidation of aminopyrine went to completion within 5 min and was inhibited by sodium azide. When EHP was added to catalase prior to the addition of aminopyrine, the ESR signal intensity of the aminopyrine free radical and the concentration of formaldehyde did not increase to appreciable values. This retardation of the oxidation of aminopyrine was considerably relieved by previously adding sodium azide to catalase. The rate of EHP-supported oxidation of methanol was comparable to that of aminopyrine. CHP previously added to catalase inhibited the EHP-supported oxidation of aminopyrine, whereas it did not inhibit that of methanol. The present results suggest that the active site of catalase for the EHP-supported oxidation of aminopyrine is different from that for the oxidation of methanol.

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The reversible hydrolysis of β-arylaminoacrolein to form arylamine and malonaldehyde was studied kinetically. The catalytic coefficient of hydronium ions (k^H+) and dissociation constant of the conjugate acid of β-arylaminoacrolein (K^BH+) were evaluated. Hammett plots for k^H+ and for K_BH+ were linear. The values of log k^H+ and pK^BH+ were expressed by the equations log k^H+=1.38σ-2.81 and pK_BH+=-1.20σ+0.90, respectively. The reversible hydrolysis of malonaldehyde dianil to form β-arylaminoacrolein and arylamine was examined in relation to that of β-arylaminoacrolein. The preparation of β-arylaminoacrolein by hydrolysis of malonaldehyde dianil was achieved under weakly acidic conditions.

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A systematic separation of a saponin fraction of the root of Bupleurum falcatum L. furnished seven new saponins, i.e., five monoacetylsaikosaponins (15-18, 20) and saikosaponins-e (19) and -f (21), besides the known saikosaponins-a, -b₂, -b₄, -c, and -d. α-Spinasteryl β-D-glucoside (22) was also isolated. The structures of these new saponins were determined by means of carbon-13 nuclear magnetic resonance spectroscopy.

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A series of α-isocyanoacrylic acid derivatives were prepared via the α-formylaminoacrylic acid derivatives, which were obtained by the reaction of isocyanoacetic acids and carbonyl compounds, in order to examine their antimicrobial activities. The structureactivity relationships are presented ; it was found that (Z)-α-isocyanoacrylic acid esters possessing halogeno phenyl or thienyl groups exhibited fairly strong antifungal activities. Of these, (Z)-methyl α-isocyano-β-(2-thienyl) acrylates (5s and 5u) showed the highest activity (1.56μg/ml MIC) against Tricophyton mentagrophytes.

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Various dimethyl 3-substituted pyrrole-2, 4-dicarboxylates (3) were synthesized by the reaction of methyl isocyanoacetate (2) with methyl α-isocyanoacrylates (5) in the presence of base. This type of reaction was also applicable to the preparation of 3-substituted pyrrole-2, 4-dicarboxamides (10) by employing appropriate amide compounds (8) or (9) and (12) as reactants. Hydrolysis followed by decarboxylation of the pyrrole diester compounds (3) gave 3-substituted pyrroles (14) in good yields. A series of these compounds (14) showed antiinflammatory activities against carrageenan-induced rat paw edema. Among the compounds tested, 3-(2-chlorophenyl) pyrrole (14d) was found to be more potent than mefenamic acid.

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Total syntheses of (±)-fawcettimine (1) and (±)-8-deoxyserratinine (3) have been accomplished. Selective hydrogenation of the conjugated nitrile (6) over (Ph₃P)₃RhCl, followed by reduction with LiAlH₄ and treatment of the product with N₃CO₂-tert-Bu yielded the carbamate (8). Successive treatment of 8 with Na-liquid NH₃, the Jones reagent, N-hydroxysuccinimide-DCC, CF₃CO₂H, and n-Bu₃N in CH₃CN afforded the nine-membered lactam (18). Reduction of 18 with LiBH₄ gave the epimeric alcohols, 22 and 23. Both 22 and 23 were converted into the same ketone (28) via the same sequence of reactions ; reduction with LiAlH₄, acylation with (CF₃CO)₂O-pyridine, selective hydrolysis with 0.2N KOH-MeOH, and Jones oxidation. Epoxidation of 28 gave the epimeric epoxides, 29 and 30. The epoxide (29) was successively treated with BF₃·Et₂O, the Jones reagent, H₂-5% Pd/C, and 1N KOH-MeOH to provide (±)-fawcettimine (1). The other epoxide (30) was converted into (±)-8-deoxyserratinine (3) by successive treatments with 1N KOH-MeOH, the Jones reagent, and NaBH₄.

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The chemical correlation between 5α-methyl-trans-clerodane diterpenes and 5β-methyl-cis-clerodane diterpenes was investigated. Attempts to correlate a trans-clerodane [e.g. methyl kolavenate (1)] with a cis-clerodane by virtue of i) photoisomerization of a 19-nor-4-keto derivative (6) of 1 and ii) photoisomerization of a related transhydrindanone derivative (14=18), were unsuccessful. However, an interrelation, by virtue of photolysis of a 19-nor-4-keto derivative (26) of cis-clerodane [e.g. linaridial (19)] leading to 6, was successful. This is the first report of a chemical correlation between cis-and trans-clerodane diterpenes. The stereochemical course of the photoisomerization observed for cis-19-nor-4-ketone (26) leading to its trans isomer (6) is discussed.

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The ¹³C NMR spectra of thirteen dibenzocyclooctadiene lignans, isolated from the iruits of Schizandra chinensis BAILL. (Schizandraceae), were analyzed and their carbon shifts assigned. Several important chemical shift trends are described.

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Three new dibenzocyclooctadiene lignans named (-)-gomisin K₁ (1) and (+)-gomisins K₂ (2) and K₃ (3) were isolated from the fruits of Schizandra chinensis BAILL. (Schizandraceae). Their structures were elucidated on the basis of chemical and spectral studies.

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Details of the separation of the metabolites (I-V) of Chaetomium thielavioideum are presented. The structure of a new mycotoxin named chaetochromin was studied by physical method (ultraviolet, infrared, ¹H- and ¹³C-nuclear magnetic resonance (NMR), and mass spectrum) and it was identified as the bis (naphthodihydropyran-4-one (II). The assignment of the ¹³C-NMR signals was largely achieved with the aid of the two-and three-bond spin-spin couplings between ¹³C and ¹H.

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Reactions of 2-chloromethylquinoline (1), its N-oxide (2) and their nitro derivatives with the sodium salt of 2-nitopropane were investigated. O-Alkylation occurred with 1 and 2, giving 2-quinolinecarboxyaldehyde (5 : 11%) and its N-oxide (6 : 10%). The reaction of 2-chloromethyl-5-nitroquinoline (3b) gave both the O-alkylation product, 5-nitro-2-quinolinecarboxyaldehyde (7 : 21%), and the C-alkylation products, 2-(2-methyl-2-nitropropyl)-5-nitroquinoline (8b : 24%) and 2-(2-methyl-1-propenyl)-5-nitroquinoline (9b : trace). In the reactions of the 6-nitro (3c) and 8-nitro (3d) derivatives of 1, the 2-(2-methyl-2-nitropropyl) quinolines (8c : 86% and 8d : 63%) were predominantly formed. In contrast, the reactions of the 4-nitro (4a), 5-nitro (4b) and 6-nitro (4c) derivatives of 2 produced the corresponding 2-(2-methyl-1-propenyl) quinoline N-oxides (11a : 53%, 11b : 20% and 11c : 66%) as main products, accompanied by small amounts of the 2-(2-methyl-2-nitropropyl) compounds (10a : 20% and 10b : 17%).

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The influence of food on the bioavailability of phenytoin was studied. A balanced meal enhanced the bioavailability significantly. A high lipid meal, however, resulted in larger inter-subject variation in bioavailability. Phenytoin-polyvinylpyrrolidone coprecipitate was administered with and without the balanced meal. The bioavailability of phenytoin administered in this form was enhanced markedly and was not greatly influenced by food intake.

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A hexanucleotide and an octanucleotide corresponding to tRNA^Met_f bases 41-46 and 47-54 were synthesized by stepwise addition of mononucleotides. The octanucleotide is the largest oligoribonucleotide synthesized by this method. A pentanucleotide (bases 61-65) and a hexanucleotide (bases 66-71) were synthesized via partially triesterified intermediates. The deblocked products were purified by ion-exchange chromatography and characterized by enzymatic hydrolysis. These oligonucleotides were used as substrates in joining reactions with RNA ligase.

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The reaction of 1-morpholino-1-cyclohexene 2 with 3-acetyl-2-hydroxy-6-methyl-4H-4-pyranone 1 gave a condensation product 3, which was subsequently transformed into the 4-pyrone 4, the β-triketone 10 and the phenol 12. The reaction of 2 with 7-chloro-2, 2-dimethyl-2H, 4H, 5H-pyrano [4, 3-d]-1, 3-dioxin-4, 5-dione 13 gave three condensation products, 14, 15 and 16.

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Thermolysis of 4-acetoxymethylene-2-[2-benzyloxy-2-(5-methoxy-3-methylbenzo-cyclobuten-1-yl] ethyl-2-methylcyclopentan-1, 3-dione 1-ethylene ketal (21) gave the stachane-type tetracyclic compound (24), whose deketalization afforded 26, a potential synthetic intermediate to the quassinoid klaineanone (1).

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Phenylalanine-1-¹⁴C, -2-¹⁴C and -3-¹⁴C, and malonic acid-2-¹⁴C were efficiently incorporated into mangiferin (1) in Anemarrhena asphodeloides. In the case of feeding with phenylalanine-1-¹⁴C, -2-¹⁴C and malonic acid-2-¹⁴C, the radioactivity of 1 was localized in the phloroglucinol ring. Furthermore, cinnamic acid-3-¹⁴C and p-coumaric acid-2-¹⁴C were also incorporated into 1 and isomangiferin (2), but benzoic acid-, p-hydroxybenzoic acid-and protocatechuic acid-(carboxyl-¹⁴C) were essentially not incorporated into 1 or 2. In addition to the above data, doubly labelled p-coumaric acid was incorporated into 1 without change of the T/¹⁴C ratio. These results show that the aglycone of 1 and 2 was biosynthesized from p-coumarate (C₆-C₃) and two malonates (C₄).

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A benzophenone, maclurin-1, 3, 5-¹⁴C₃ (3), was efficiently incorporated into C-glucosylxanthones [mangiferin (1) and isomangiferin (2)] of Anemarrhena asphodeloides without randomization, but the labelled aglycone of 1 and 2 (1, 3, 6, 7-tetrahydroxyxanthone-2, 4, 9a-¹⁴C₃) (4) was essentially not incorporated. Furthermore, the incorporation of phenylalanine-3-¹⁴C into 1 and 2 was clearly suppressed by the addition of non-labelled maclurin (3) to the precursor solution. These results indicate that C-glucosylation of 1 and 2 occurs at the stage of maclurin (3), prior to the formation of the xanthone nucleus, and that 1 and 2 may be biosynthesized via 3-C-glucosylmaclurin (6). A biosynthetic route is proposed for mangiferin (1) and related C-glucosylxanthones.

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Several homoisoflavonoidal compounds, namely the monomethyl ethers ((IIIb) and (IVb)) of methylophiopogonones A and B, isoophiopogonone A monomethyl ether (VIIIb) and desmethylisoophiopogonone B (IXa), which were derived from the constituents of Ophiopogonis tuber (tuber of Ophiopogon japonicus KER-GAWLER var. genuinus MAXIM., Liliaceae), have been synthesized. The chemical and spectroscopical assignments reported in the previous papers have been confirmed by the synthesis of methylophiopogonone A (IIIa ; 5, 7-dihydroxy-6, 8-dimethyl-3-(3, 4-methylenedioxybenzyl)-chromone), methylophiopogonone B (IVa ; 5, 7-dihydroxy-3-(4-methoxybenzyl)-6, 8-dimethyl-chromone), isoophiopogonone A (VIIIa ; 5, 7-dihydroxy-8-methyl-3-(3, 4-methylenedioxybenzyl)-chromone) and desmethylisoophiopogonone B (IXa ; 5, 7-dihydroxy-3-(4-hydroxybenzyl)-8-methylchromone).

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3-Acetyl and 3-decanoyltetramic acids with various substituents at the 5-position and their copper complexes, which possess a tricarbonylmethane structure, were prepared and tested for antimicrobial activity. 3-Decanoyltetramic acid derivatives and their copper complexes inhibited the growth of Bacillus subtilis and Staphylococcus aureus, but did not inhibited the growth of gram-negative bacteria and molds. 3-(1-Iminoethyl)-tetramic acids and their copper complexes were synthesized and tested for inhibitory activity towards chlorophyll development in plants.

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The adsorption of Methylene Blue on magnesium silicate prepared by three different methods at 30°and 90°was investigated in order to elucidate the mechanism of adsorption of Methylene Blue on porous magnesium silicate. The adsorption isotherm of Methylene Blue was well described by the Langmuir equation. The amount of Methylene Blue adsorbed on porous magnesium silicate was dominated by its total pore volume. It is suggested that the pores with radius smaller than 14.5Å are completely filled with Methylene Blue, while the pores with radius larger than 15Å remain partially unfilled.

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The synthesis of four fragments from dipeptide to pentapeptide, corresponding to amino acids 32 to 36 of thymopoietin II, and four analogs is described, together with their effects on E-rosette forming cells in the uremic state. After incubation with amounts of H-Arg-Lys-Asp-Val-Tyr-OH (residues 32-36) varying from 100 to 200 μg/ml of cell suspension, maximum T-cell rosette formation ranged from 65 to 73% compared with 50 to 52% without the peptide. The activity of H-Arg-Lys-Glu-Val-Tyr-OH was lower than that of H-Arg-Lys-Asp-Val-Tyr-OH. The other fragments and analogs had no effect on the E-rosette formation-inhibiting activity of uremic serum at a dose of 200 μg/ml

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High-performance liquid chromatography combined with electrochemical detection was applied for the determination of estriol in human urine obtained during pregnancy. Estrogens were extracted with ether, chromatographed on a reversed-phase C-18 column with a mobile phase of methanol-water-perchloric acid mixture, and detected electrochemically at 1.1 V vs. Ag/AgCl. The minimum detectable quantity of estriol was 10 ng. Within-run precision was better than 3% for the whole procedure.

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An improved procedure which avoids prolonged reaction at high temperature and handling under reduced pressure was found for the reduction of heteroaromatic and aromatic nitro compounds with aqueous titanium (III) chloride.

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The spectrophotometric determination of silver (I) with 5-p-dimethylaminobenzylidene-2-thiobarbituric acid (DABTB) was studied and two simple and rapid methods are proposed. One is based on photometry of the DABTB-Ag (I) complex in ethanol-buffer (pH 6) solution (method A), and the other is based on measurement of the decrease in absorbance of DABTB due to the complex formation (method B). Beer's law holds over the range of 0.04-2 μg/ml of silver (I) at 400 nm in method A, and 0-35 μg of silver (I) at 484 nm in method B. The molar extinction coefficient of the complex is 2.5×10⁴·1·mol^-1·cm^-1 in method A. Hg (I, II), Au (III), Pd (II), Pt (IV), and various anions such as Br^-, Cl^-, I^-, SCN^-, CN^-, S₂O₃^2-, and S^2- interfered with the determination. These methods were successfully applied to the determination of silver (I) in commercial preparations such as silver nitrate eye lotion and silver protein.

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The reactions of N, N, 9-trialkyladenines (II) with alkyl halides in N, N-dimethylacetamide gave N, N, 3, 9-tetraalkyladeninium halides (IV) in good yields. N, N, 3-Trialkyl-adenines (III) underwent the alkylation more smoothly to provide an alternative synthesis of IV.

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A convenient synthesis of 1, 2, 3, 4, 6, 7, 12, 12b-octahydroindolo [2, 3-a] quinolizine (1) is described. The condensation of tryptamine (2) with diethyl (2-formylethyl) malonate (3a), followed by treatment with alkali, gave the lactam ester (5a). Decarbethoxylation of 5a with LiCl-H₂O-Me₂SO afforded the lactam (8a), which was reduced with LiAlH₄ to give the indoloquinolizine (1). The lactam (8b) which has an ethyl group at C₃ was prepared from tryptamine (2) and diethyl ethyl (2-formylethyl) malonate (3b) instead of 3a.

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Three metabolites of the antibacterial agent, piromidic acid (8-ethyl-5, 8-dihydro-5-oxo-2-(1-pyrrolidinyl) pyrido [2, 3-d] pyrimidine-6-carboxylic acid), were synthesized in order to confirm their structures, i.e., 2-(3-hydroxy-1-pyrrolidinyl)-(4), 2-(2-hydroxy-1-pyrrolidinyl)-(8), and 2-(3-carboxypropylamino)-8-ethyl-5, 8-dihydro-5-oxopyrido [2, 3-d]-pyrimidine-6-carboxylic acids (13). Compounds 4, 8, and 13 were identified with the metabolites designated as A, B, and I, respectively, on the basis of their IR, UV, MS, and NMR spectra. 8-Ethyl-5, 8-dihydro-2-(3- and 4-hydroxypiperidino)-5-oxopyrido [2, 3-d] pyrimidine-6-carboxylic acids (6a and 6b) as well as the O-formyl (5a), -acetyl (5b), -benzoyl (5c), and -methanesulfonyl (5d) derivatives of 4 were prepared and tested for antibacterial activity. Of the compounds discussed in this paper, 4 was the most active, particularly against gram-negative bacteria.

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Hydrolytic reactions of triazolobenzo- and triazolothienodiazepines (estazolam and etizolam) as well as a thienodiazepine (clotiazepam) were studied spectrophotometrically. Cleavage reactions of the azomethine bonds of estazolam and etizolam were reversible and the open-ring compounds were in equilibrium with the closed-ring compounds (protonated forms of the parent drugs). However, little spectral change was observed in clotiazepam. The rate of ring-closure reaction was greater than that of ring-opening reaction in estazolam whereas the opposite was the case in etizolam. The activation energies of the forward and reverse reactions were obtained from Arrhenius-type plots. In addition, the pK_a value of etizolam was determined.

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Hydralazine reacts with nitrite ion under an acidic condition at 37°to form tetrazolo-[5, 1-a] phthalazine (Tetra-P) almost quantitatively. Without extraction, Tetra-P was determined sensitively by high-performance liquid chromatography. This method is more specific than the conventional methods for the determination of nitrite ion.

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The d-tertiary hydroxy metabolite, which was isolated from rat urine after oral administration of 3, 3, 3-d₃-l-2-(2-isopropylindan-5-yl) propionic acid (IIPA), was confirmed to retain the intact CD₃ group on the basis of the MS and NMR spectral analyses. This finding is not compatible with the exomethylene intermediate mechanism proposed for the same epimerization reaction of 2-(4-isobutylphenyl) propionic acid (ibuprofen) in human.

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The structure of euglobal-III (1), a novel granulation inhibiting agent from Eucalyptus globulus LABILL., has been determined on the basis of physicochemical data and X-ray crystallographic analysis.

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A new flavone derivative, containing condensed dihydrochalcone partial structure named kuwanon G, was isolated from the root barks of the cultivated mulberry tree (a variety of Morus alba L.). The structure was shown to be 1 on the basis of chemical and spectral data. The compound (1) to rabbit (1 mg/kg, i.v.) produced a significant hypotension.

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