The afferent impulses from the aortic arch baroreceptor in the left aortic nerve of rabbits were recorded in situ and in the perfused preparation. Epinephrine, acetylcholine, lyoniol-B and ouabain excited the baroreceptor in both preparations. Propranolol and N-propyl ajmaline decreased the rate of afferent impulses in the in situ preparation, but had no influence in the perfused preparation. Possible mechanisms of these drugs affecting the impulse activity in the aortic nerve are discussed.

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The chemical determinations of piromidic acid (PA, 5, 8-dihydro-8-ethyl-5-oxo-2-pyrrolidinopyrido [2, 3-d] pyrimidine-6-carboxylic acid=pyrrolidino-PPA) and its metabolites in blood, urine and bile of rats receiving a single oral (100mg/kg) or intravenous (25mg/kg) dose of PA were performed utilizing thin-layer chromatographic separation, followed by ultraviolet spectroscopic determination. The same determinations were also made for human subjects receiving oral PA of 1 g. The following results were obtained : (1) PA was rapidly metabolized to M-II (2-hydroxypyrrolidino-PPA) and M-V (3-hydroxypyrrolidino-PPA) in both species after oral and intravenous administrations. (2) Blood levels of M-II, M-IV (3-hydroxycarbonylpropylamino-PPA), unchanged PA and M-V in order of decreasing amounts in rats all reached their peaks 2 to 3 hr after oral administration. On the contrary, blood levels of M-III (amino-PPA) were too low to be determined. Analogous results were also obtained in humans. (3) An average 24-hr biliary excretion in rats receiving intravenous PA was about 63% of the dose and a major metabolite was M-IV, accounting for about 23% of the dose. (4) In man, an average recovery in 24-hr urine was about 42% of the dose after oral administration. M-IV, M-V, M-II, M-III, PA and glucuronides were excreted in order of decreasing amount. In rats, the similar results were obtained after oral and intravenous administrations. (5) The antibacterial activity in blood, bile and urine was found to be associated almost entirely with M-II, M-V, and unchanged PA in both species after oral or intravenous administration, with significant predominance of M-V in the urine. Urinary or biliary levels of total active materials were found to be high enough to inhibit Escherichia coli.

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It was demonstrated that acetanilide hydroxylation in man is saturated by as small as 0.5 g dose. Subjects ingested low dose (100 mg) and high dose (500 mg) of acetaminophen and acetanilide. Total acetaminophen (free and conjugated) excreted in urine was determined. Ratio of amount excreted (RAE) between two dose levels was calculated. Saturation of pharmacokinetic process was verified by the value of regression coefficient of RAE to t.

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2-Thiopicolinoanilide and its meta-and para-substituted derivatives were synthesized. These thioanilides were converted readily to the corresponding O-amides by hydrogen peroxide in alkaline solution. The oxidations of the thiopicolinoanilides by use of a large excess of hydrogen peroxide were kinetically carried out and the activation energies were determined. The small increase in the rates is attributed primarily to the electron-attracting effect of the substituents. On the other hand, these acid dissociation constants were measured in 20% ethanol-water at 20° by spectrophotometry and fitted the Hammett equation with the use of σ (ρ=1.4), but the p-carboethoxy group deviates from the straight line because of its much lower pK_a (8.42) value. In the reaction between 2-thiopicolinoanilides and o-aminophenol, the yield of 2-(2-pyridyl) benzoxazole increased with increasing electron-attracting effect of the substituent in the order of the observed acidity of thioanilides.

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Reactions of 4-alkylpyrimidines with formamide in the presence of phosphoryl chloride (called the modified Vilsmeier reaction) were described. 4-Methylpyrimidine derivatives (I, III) gave 4-pyrimidinylpyrimidines (II, IV) respectively but 4-methylenepyrimidine derivatives (V, VII) afforded 5-hydroxy-6-[4-(5-methylpyrimidinyl)]-2, 4-diaza-2-heptenal (VI) or bis (5, 6, 7, 8-tetrahydro-8-quinazolinylidenemethyl) amine (VIII) and 8-formylaminomethinyl-5, 6, 7, 8-tetrahydroquinazoline (IX).

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The pharmacokinetic studies of piromidic acid (PA, 5, 8-dihydro-8-ethyl-5-oxo-2-pyrrolidinopyrido [2, 3-d] pyrimidine-6-carboxylic acid) were performed in rats after intravenous administration. Two compartment model, the central and peripheral compartment was adopted and the central compartment was connected to four metabolite compartments in branched metabolic pathways, totaling eleven parameters involved. Each parameter was determined by conjunction of graphical and mathematical methods using the experimental data on blood levels along with urinary and biliary excretions in rats receiving PA or each metabolite. Calculated blood levels of PA or its metabolites thus obtained were found to be reasonable. The peripheral compartment is ascribed to enterohepatic circulation of PA. This pharmacokinetic model may possibly applied on human subjects, since urinary metabolic patterns were similar in rats and human subjects receiving PA.

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A sink in vitro drug elution system was applied to characterize the mechanisms and rates of drug release of progestins from silicone capsules. A zero order (constant) drug release profile was observed. The rate of drug release was found to be a linear function of the partition coefficient of drug from silicone polymer to elution medium. The subcutaneous implantation of such delivery device in heifers resulted an in vivo release rate in agreement with the value predetermined on the basis of in vitro data. The in vivo drug release rates observed for all the four progestins investigated were found to be computable from the physico-chemical parameters following a theoretical expression. The thermodynamics of the drug release process was also analyzed and found to be in agreement with experimental observations.

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6, 7, 8, 9-Tetrahydro-5H-imidazo [1, 5-a] [1, 4] diazepine derivatives (IV) were synthesized by the reaction of formalin with 1-γ-aminopropylimidazole derivatives (III) prepared by cyanoethylation and then catalytic hydrogenation of the imidazole derivatives (I).

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Alkaline hydrolysis of N-benzoyloxy-N-methyl-4-aminoazobenzene (II) in the presence of ascorbic acid gave N-hydroxy-N-methyl-4-aminoazobenzene (I) which has been estimated as proximate compound of hepatocarcinogenic N-methyl-or N, N-dimethyl-4-aminoazobenzene. Several acyl derivatives of I including acetyl derivative were synthesized. Alkaline treatment of I or II in the presence of dissolved oxygen, yield 4-nitroazobenzene (IV) and 4, 4′-bisphenylazo-azoxybenzene (V), probably through intermediate forms, nitron and hydroxylamine compound.

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Pelletierine which was established to be a precursor in the biosynthesis of cernuine (1), was converted into the quinolizidine (22), whose N-chloro derivative (27) was irradiated with 300 W high pressure mercury lamp in ether in the absence of any strong acid to readily afford the entitled compound (3) as the free base with no base treatment. The present photocyclization is thus different from the known Hofmann-Loeffler reaction in several respects, which are demonstrated for discussion.

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Methyl 14-oxo-5α, 8β, 9α-podocarp-15-oate (4) is synthesized from methyl 13-isopropyl-7-oxopodocarpa-5, 8, 11, 13-tetraen-15-oate (5) by combination of the following processes : nitration at the 14-position ; conversion of the nitro group into the hydroxy group ; deisopropylation ; reductions of the enone function and C ring ; oxidation of the 14-hydroxy group to the oxo group.

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The route of in vivo formation of 4-formylaminoantipyrine which is a new metabolite of aminopyrine was examined. As a result of examination by gas chromatography-mass spectrometry and ¹³C-NMR after oral administration of ¹³C-labeled aminopyrine to man and experimental animals, formylamino group was formed by oxidation of N-methyl side chain of aminopyrine.

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5-Amino-6-hydroxy-2-methlythiopyrimidine-4-carboxamide (VII) was prepared from methyl 6-hydroxy-2-methylthiopyrimidine-4-carboxylate (V) by bromination, followed by amino-amidation. VII was also prepared by a similar treatment of 6-hydroxy-2-methylthiopyrimidine-4-carboxamide (VIII) which was synthesized by half-amidation of sodium salt of ethyl methyl oxalacetate (IV), followed by treatment with S-methylisothiourea sulfate. 4, 8-Dihydroxy-2-mercapto-6-methylthio-pyrimido [5, 4-d] pyrimidine (I) was synthesized with quantitative yields by reacting VII with sodium or potassium ethylxanthogenate or with diethylammonium N, N-diethyldithiocarbamate in suitable solvents, such as pyridine, water, etc., under refluxing condition. I was converted to 4, 8-dihydroxy-2, 6-dimercapto-pyrimido [5, 4-d] pyrimidine (II) by treating sodium salt of I in ethylene glycol at about 125° in passing of hydrogen sulfide.

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In order to obtain the specific antiserum used for radioimmunoassay of estetrol a new hapten-carrier conjugate was prepared from 6-ketoestetrol O-carboxymethyloxime by coupling with bovine serum albumin employing the mixed anhydride technique. The specificity of anti-estetrol antiserum elicited in the rabbit by immunization with this antigen was tested by cross-reaction studies with the closely related steroids. The results indicated that highly specific antiserum to estetrol would be produced by antigen whose steroidal moiety is coupled to a protein through the position remote from the inherent functional groups.

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An improved synthesis of 6, 7endo-dimethyl-1-(3-hydroxyphenyl)-6-azabicyclo [3, 2, 1]-octane (10c), a new analgetic agent with a low addiction liability, is described. Grignard reaction of 3-ethoxy-2-cyclohexen-1-one (1) with m-methoxyphenylmagnesium bromide gave the α, β-unsaturated ketone (2b). Hydrocyanation of the latter followed by methanolysis yielded the keto ester (5b). The bicyclic lactam (8b), a key intermediate in the original synthesis was obtained by reductive amination of 5b with methylamine. As a result of this sequence of reactions, 10c could be obtained in 7 steps from 1 in 42% overall yield. By an application of this new method, a number of 1-phenyl-6-azabicyclo [3, 2, 1] octane derivatives with various substituents on benzene ring (10d-k), nitrogen (31), and C₈ (39-46) have been prepared for pharmacological evaluation.

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Direct introduction of bromine into the A-ring of the phenacylidene derivatives of l-abietic acid (1) was developed and it was applied to the conversion of 1 into teideadiol (2), a naturally occurring diterpene with a hydroxy group on the A-ring of its abietane skeleton.

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Canthin-6-one (I), canthin-6-one 3-oxide (III) and new alkaloid, 1-methoxycanthin-6-one (II) were isolated from the wood of Ailanthus altissima SWINGLE (Simaroubaceae). The structure of II was elucidated by spectroscopic studies and chemical evidences.

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The bulbs of Lycoris sanguinea MAXIM. var. kiushiana MAKINO (Amaryllidaceae) were found to contain a new phenolic alkaloid, sanguinine (I), as well as lycorine (II) and galanthamine (III). Sanguinine (I), C₁₆H₁₉O₂N, was established to be O-demethyl-galanthamine. Pretazettine (VII) was isolated from the bulbs of Lycoris radiata HERB. (Amaryllidaceae).

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The reaction of diketene with N-arylhydroxylamine (Ia-g) gave N-hydroxyaceto-acetanilide derivative (VI), as a main product, besides the formation of azobenzene derivative (II), azoxybenzene derivative (III), 2-methylindole derivative (IV), and 2-aryl-5-methyl-4-isoxazolin-3-one (V). In the cases of Ia, Ic and Id, the reaction gave 2'-acetonyl-acetoacetanilide derivative (VIIa, c, d), which on hydrolysis with alkali was transformed to 1, 5-dihydro-4-methyl-2H-1-benzazepin-2-one derivative (VIIIa, c, d). In the formation of 2-methylindole derivative from Ic and Ie, reactions proceeded regiospectifically to give 2, 6-dimethylindole (IVc) and 6-chloro-2-methylindole (IVe), respectively. Similarly in the formation of compound VII from Ic, the reaction gave a sole product (VIIc). The reaction mechanisms are also discussed in connection with the structural elucidations.

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Two new polyoxypregnane derivatives, deacetyltomentosin (12β-O-tigloyl-tomen-togenin) and tomentidin (12β-O-acetyl-20-O-cinnamoyltomentogenin), were isolated from the stem of Marsdenia tomentosa. Deacetyltomentosin is a monoester possessing the tomentogenin skeleton to be isolated from the Asclepiadaceae plants for the first time.

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Absorption characteristics of buformin and phenformin, the hypoglycemic biguanides, were studied in the in situ rat small intestine. It was suggested that the small intestinal absorption of these biguanides is probably mediated by passive process. The absorption of these biguanides from the ileum was more rapid than that from the jejunum, and such the difference was not associated with the accumulation characteristic of the drugs in the intestinal tissues. From observations on the release of the components such as membrane phosphorus, lipid phosphorus, and protein from the jejunum and ileum, it was suggested that the more rapid absorption of these biguanides from the ileum would be attributable to that the release of membrane components from the ileum was much larger than from the jejunum, resulting in a much increased permeability of the ileum to the drugs.

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An useful procedure for the synthesis of 2-substituted 1, N⁶-etheno-adenosine-3', 5'-cyclic phosphates by ring closure of 3-β-D-(3', 5'-cyclic phospho)-ribofuranosyl-4-amino-5-(imidazol-2-yl)-imidazole (II), under relative mild conditions, is reported. Treatment of the compound II with bromine cyanide, triethyl orthoacetate, 1, 1'-carbonyldiimidazole and carbon disulfide gave 2-amino-, 2-methyl-, 2-hydroxy-, and 2-mercapto-1, N⁶-etheno-adenosine-3', 5'-cyclic phosphate (c-AMP), respectively. Moreover, several 2-alkylmercapto-, 2-benzylmercapto-, and 2-bromo-1, N⁶-etheno-c-AMP were synthesized from 2-merc apto-1, N⁶-etheno-c-AMP. 2-Methoxy-, 2-azido-, 2-dimethylamino-1, N⁶-etheno-c-AMP were synthesized from 2-bromo-1, N⁶-etheno-c-AMP. The fluorescent and ultraviolet spectra of 2-substituted 1, N⁶-etheno-c-AMP are tabulated.

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The p-methoxybenzenesulfonyl (MBS) group was used to protect the ω-guanidino function in arginine and was found to be more easily and completely removed by treatment with methanesulfonic acid and borontristrifluoroacetate (BTFA) than the p-toluene-sulfonyl group. In order to evaluate the usefulness of this new protecting group in peptide synthesis, bradykinin and tuftsin were prepared by using the MBS group.

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The relationships between the cell wall glycan synthesis and hydrolysis by mycelial crude enzyme were studied. The crude enzyme indicated some hydrolytic activities to the synthesized β-glucan or chitin-like substance under the optimum conditions for respective glycan synthesis. The most of all enzyme activities were found in the microsomal fraction (glucan synthetase and chitin synthetase) and the soluble fraction (β-glucanase and β-N-acetylglucosaminidase). The activities of the β-glucan synthetase or chitin synthetase contained in microsomal fraction were not affected by addition of uridine diphosphate (UDP)-N-acetylglucosamine (into β-glucan synthetic system) or UDP-glucose (into chitin synthetic system). While the activities of the β-glucanase or β-N-acetylglu-cosaminidase contained in the soluble fraction were inhibited by addition of UDP-N-acetylglucosamine (into β-glucanase assay system) or UDP-glucose (into β-N-acetylglucosaminidase assay system). Therefore, when the mycelial crude enzyme was used as synthetase, it is evident that UDP-N-acetylglucosamine (precursor of chitin) in the β-glucan synthetic system of UDP-glucose (precursor of β-glucan) in the chitin-like substance synthetic system is not a stimulator of synthetase but an inhibitor of hydrolytic enzymes. The possible role of these phenomena at the time of cell wall growth was discussed.

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Heating of 3-phenyl-, 3-methyl, and 3-chloro-6-[2-(2-methylallyl) phenoxy] pyridazine in diethylaniline or without a solvent afforded 2-substituted-9a-methyl-1, 9a-dihydroxanthenes, which are previously unknown group of compounds. The mechanism of this reaction may be explained by an intramolecular cycloaddition between pyridazine nucleus and the allylic side chain to give the (4+2)π adduct followed by N₂ elimination. Similarly, cyclization of 1-phenyl-4-[2-(1-methylallyl)-1-naphthyloxy] phthalazine gave 5-phenyl-6a-methyl-6a, 12a-dihydro-7H-benzo [c] xanthene.

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Intramolecular cycloaddition of 3-phenyl-6-(2-allylphenoxy) pyridazines afforded 2-phenyl-1, 9a-dihydroxanthenes, while 3-methyl-6-(2-allylphenoxy)-, and 3-(2-allylphenoxy) pyridazines gave mixtures of dihydroxanthenes. Depending upon condition, 3-chloro-6-(2-allyl-4-alkoxycarbonylphenoxy) pyridazines gave rise to the corresponding 1, 9a-, and 1, 4-dihydroxanthenes along with 2-alkoxycarbonylxanthenes.

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A new depsidone named oxyphysodic acid (2), which has been known to occur often concomitantly with physodic acid (1) in the lichen belonging to the genus Hypogymnia (Parmeliaceae) and also in the lichen of several other species, has been isolated from the lichen Hypogymnia enteromorpha (ACH.) NYL. The structure (2) possessing the pyrogalloltype oxygenation pattern has been established for oxyphysodic acid on the basis of chemical and physicochemical evidence.

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Two new depsidones named vittatolic acid (4) and 2'-O-methylphysodic acid (5) have been isolated from the lichen Hypogymnia vittata (ACH.) GAS. along with physodic acid (1), atranorin (2), oxyphysodic acid (3), zeorin (6), and ergosterol peroxide (7). Vittatolic acid (4) is the first optically active depsidone possessing a secondary hydroxyl in the side chain. The plain structure of vittatolic acid has been clarified on the basis of physicochemical evidence and the conversion to physodic acid (1), and the absolute configuration at the asymmetric carbon in the side chain of 4 follows from the application of the Horeau's method and the Brewster's benzoate rule. The structure of 2'-O-methylphysodic acid (5) has been determined on the basis of chemical and physicochemical evidence.

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Kanzakiflavone-2 (I), a new flavone has been isolated from the ethereal extract and three known compounds, iridin (VI), mangiferin (VII) and isomangiferin (VIII) were isolated from the n-butanolic extract of Iris unguicularis POIR. respectively. The structure of kanzakiflavone-2 (I) has been determined as 5, 4'-dihydroxy-6, 7-methylenedioxyflavone by chemical and spectral means.

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The configuration of C₃-methyl group in each isomer of 2-oxo-3-methyl-trans-octahydroindole (VIIa and VIIb) was determined by the evidence of their NMR spectra and the conformational analyses using Dreiding model. Accordingly, the C₃-ethoxycarbonyl group in 2-oxo-3-ethoxycarbonyl-trans-octahydroindole (I), which was obtained by the reaction of meso-cis-cyclohexenimine and diethyl malonate, was proved to have cis-configuration in relation to C_3a-H. The methylation of I and its N-benzylsulfonyl derivative (X) gave Vb, and XI of which C₃-methyl group had trans-configuration to C_3a-H, respectively. On the other hand, the methylation of 2-oxo-1, 3-diethoxycarbonyl-trans-octahydroindole (XII) gave also C₃-methyl derivative (XIII), but the configuration of C₃-methyl group of XIII was cis to C₃a-H.

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Solvate formation of griseofulvin with benzene and dioxane was confirmed by differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and X-ray diffractometry. Combining ratios of the two solvates were determined by TG to be 1 : 2 and 2 : 1 with respect to griseofulvin and benzene, and griseofulvin and dioxane, respectively. From data by solubility measurements and by various thermal methods of analysis such as DSC, freezing point determination by cooling curve method, the phase diagrams of the systems between benzene and griseofulvin, and between dioxane and griseofulvin were constructed. Also, thermodynamic properties of these solvates were investigated. It was found that the transition temperatures and the overall heats of desolvation were 35°and 6.3±0.2 kcal/mole of solvent for the benzene solvate, and 80-85°and 6.0±0.5 kcal/mole for the dioxane solvate, respectively. Moreover, the possibilities of these solvates for applying to particle size reduction of griseofulvin were examined. As for the benzene solvate, the free griseofulvin obtained by desolvation has a specific surface area of 7 m²/g, and a mean particle size of 0.58μ. In the case of the dioxane solvate, the specific surface area after desolvation was reached to 4.8 m²/g ; however, the desolvated particles retained their original shapes. Surface structures of the two kinds of desolvated products were examined by scanning electron microscopy. As the results, it became clear that the desolvated particles from the dioxane solvate has a stout and very porous structure, though those from the benzene solvate are the laminar aggregates composed of very easily separable primary particles.

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A pair of stereoisomers of the ring A model for daunomycinone was synthesized. The stereochemistries of isomeric α-tetralol-type intermediates and of the target compounds were discussed on the basis of spectral evidences. For all of the synthetic cis-1, 3-glycol systems related to ring A of daunomycinone were demonstrated a favorable di-axial conformation of the hydroxyls and the outside orientation of the O-H bond in the quasi-axial benzylic hydroxyl, while a quasi-equatorial conformation of the benzylic hydroxyl was found favorable for trans-1, 3-glycol system of the stereoisomers epimeric at C₁.

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The metabolism of tetracaine in rats, mice, rabbits and horses has been investigated. It was found that a considerable amount of a new metabolite was excreted in the urine of all the animals examined. The metabolite was isolated as crystals from the urine of the tetracaine-administered rabbits and horses, and was characterized as tetracaine N-oxide on the basis of analytical and spectral data.

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Reaction of benzimidazole and N-acetylbenzimidazole with diketene in acetic acid or acetic anhydride at room temperature resulted in the formation of 2-acetonyl-1, 3-diacetyl-2, 3-dihydrobenzimidazole (II), and 5-acetyl-4a, 5-dihydropyrido [1, 2-a] benzimidazol-1, 3 (2H, 4H)-dione. On the other hand, reactions of 2-ethoxycarbonylmethylbenzimidazole (XIIIa), 2-carbamoylmethylbenzimidazole (XIIIb), 2-cyanomethylbenzimidazole (XIIIc) with diketene in acetic acid at room temperature resulted in the formation of 4-substituted-3-methylpyrido [1, 2-a] benzimidazol-1 (5H)-one (XIIIa-c) in good yields, respectively.

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Mice were subjected to stress consisting of restraint and water immersion and the variation in serum glucose, serum free fatty acids (FFA), and liver glycogen concentrations and the development of gastric erosions were determined at given intervals for a period of 18 hr. In control mice which were deprived of food and drinking water, no significant variation was observed in serum glucose and FFA levels throughout the experimental period. In contrast, their liver glycogen content was virtually exhausted 9-12 hr after fasting and then began to accumulate, resuming its 6-hr value 18-24 hr after fasting. In stressed mice, serum glucose levels decreased after 1-3 hr of stress and increased thereafter, showing a significant elevation in the levels compared with its 3-hr value 18 hr after stress. On the contrary, FFA levels increased for the initial 1-3-hr period, declined 12 hr after stress, and showed a significant decrease compared with the corresponding value in the control group 18 hr after stress. Liver glycogen was practically exhausted for the first 12-hr period after stress. Thereafter, its levels increased but was still lower than those in the control group 18 hr after stress. Gastric erosions were generated after 1 hr of stress and developed with the progress of time, reaching the highest severity of erosions at the end of stress.

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Sephadex G-75 gel filtration of cytoplasmic protein with BSP in vitro yielded elution patterns characteristic of the protein sources as liver, kidney, and small intestinal mucosa of rat and rabbit. In the both species, binding of sulfobromophthalein (BSP) with Y protein was observed to be predominant in the liver, and weak or not recognized in the kidney and small intestinal mucosa, as was to be expected. On the other hand, the BSP elution with Z protein fraction was appreciable in the rabbit kidney and the rat small intestinal mucosa, and it appeared that the role of Z protein on the fate of the organic anion in the body was not so simple. Two unknown fractions, Y'and Y"protein, were recognized in the BSP elution pattern with cytoplasmic protein of the rat kidney, and Y'protein was recognized in that of the rabbit kidney and small intestinal mucosa.

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The effects of sodium chloride, sodium sulfate, and sodium iodide on the solubility of 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil, 6-mercaptopurine, and thioinosine were studied. Sodium chloride and sulfate salted-out these antimetabolites while sodium iodide salted-in them. The solubility of these antimetabolites at various temperatures was also measured. There was no indication of the transition in the stable form in the temperature range studied.

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The starting material, ethyl 7-bromomethyl-4-hydroxy-1, 8-naphthyridine-3-carboxylate (2), was prepared by the reaction of ethyl 4-hydroxy-7-methyl-1, 8-naphthyridine-3-carboxylate (1) with bromine. Condensation of 2 with 5-nitrofurfural afforded ethyl 7-[1-bromo-2-(5-nitro-2-furyl) vinyl]-4-hydroxy-1, 8-naphthyridine-3-carboxylate (3) which was subsequently hydrolized to give 7-[1-bromo-2-(5-nitro-2-furyl) vinyl]-4-hydroxy-1, 8-naphthyridine-3-carboxylic acid (4). Alkylation of 4 with alkyl iodide provided 1-alkyl-7-[1-bromo-2-(5-nitro-2-furyl) vinyl]-4-oxo-1, 8-naphthyridine-3-carboxylic acid (5 and 6). Nucleophilic displacement of bromine in 4, 5, and 6 afforded the corresponding 7-[1-alkylamino-2-(5-nitro-2-furyl) vinyl]-1, 8-naphthyridine derivative (7-14). Some members of the series display sufficient antibacterial activity in vitro against both Grampositive and Gram-negative bacteria, however, none of them was active as the model compound, 1-ethyl-7-[2-(5-nitro-2-furyl) vinyl]-4-oxo-1, 8-naphthyridine-3-carboxylic acid (15).

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Experiments were made to see the substrate specificity of purified esterase from various origins using p-nitrophenyl acetate, α-naphthyl acetate and trans-4-aminomethyl-cyclohexanecarboxylic acid esters as a substrate. And attension was focused on the influence of structural properties of trans-4-aminomethylcyclohexanecarboxylic acid esters. The hydrolysis rate of α-naphthyl acetate of p-nitrophenyl acetate differed markedly according to animal species. In all the enzymes from rats, guinea pigs, rabbits, and pigs, phenyl ester was hydrolyzed more readily than benzyl ester or alkyl ester. The hydrolysis rate of phenyl esters was affected by the steric as well as electronic effect of the substituents.

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(-)-Kaur-16-en-19-oic acid (I) is transfered by Cunninghamella blakesleeana to a series of differently hydroxylated derivatives, four compounds of which have been isolated and characterized as 7β-hydroxy-(-)-kaur-16-en-19-oic acid (II), 16-hydroxy-(-)-kauranoic acid (III), 16α, 17-dihydroxy-(-)-kauran-19-oic acid (IV) and 7β, 16α-dihydroxy-(-)-kauran-19-oic acid (V).

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A new diterpenoid, named vitexilactone (I), was isolated together with a known iridoid glycoside, agnuside, a known flavonoid, artemetine, and p-hydroxybenzoic acid from the leaves of Vitex cannabifolia SIEB. et ZUCC. (Verbenaceae). The structure of vitexilactone was established as I by the chemical and spectral examinations.

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3-Ethyl-5-bis (methylthio) methylene-2-thioxothiazol-4 (5H) one (2), which was prepared by the reaction of 3-ethylrhodanine with carbon disulfide in the presence of sodium hydroxide in dimethyl sulfoxide, reacted with nucleophilic reagents such as amines or active methylenes to give the corresponding replacement products of one or two methylthio groups in good yield.

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The crystalline form taken by sulfanilamide monohydrate depends on the concentration of sulfanilamide in the aqueous solution from which it is crystallized. Apparent heats of solution are reported for the four (anhydrous) polymorphic forms of sulfanilamide.

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Synthesis of compounds containing a novel ring system, thieno [4, 3-f] morphan, has been accomplished starting from 3-thenyl chloride derivative (1) in 3 steps.

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The pro-R hydrogen from C-1 methylene of primary allylic alcohols as geraniol and trans-cinnamyl alcohol was abstracted in cell-free system of callus induced from Cannabis sativa L.

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The title new reducing disaccharide (10) was synthesized starting from 1, 6-anhydro-4', 6'-O-benzylidene-β-lactose (1) via selective benzoylation, epoxide formation, alkaline cleavage of the epoxide, and removal of the blocking groups. This is the first reported example of isomerization of the secondary hydroxyl groups in the D-galactopyranosyl moiety of lactose.

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Optical properties of models for the ligation in cytochrome P-450 system were investigated by interaction of hemin with biologically significant thiol compounds such as cysteine and cysteine methyl ester, in the presence of such bases as pyridine, imidazol and histidine under physiological condition. It is shown that cysteine binds to ferric porphyrin to form axial S-Fe-N coordination in the presence of a base, and ferric porphyrin is easily reduced to ferrous porphyrin by an excess thiol. Under exposure of CO of these systems, the characteristic absorption band at 450 nm was observed, which is typical with cytochrome P-450·CO complex. These results would show that the model used nicely represent the reaction involved in the vicinity of heme moiety of cytochrome P-450 under physiological condition.

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A new anthrone C-glycoside, cassialoin was isolated from the heartwood of Cassia garrettiana CRAIB. (Leguminosae), a Thai drug"Sa mae sarn"being used as mild cathartics, and was elucidated as 10-hydroxy-10-C-D-glucosylchrysophanol-9-anthrone.

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