1. Urinary excretion of CHS-Na metabolites increased in rabbits and rats after prolonged administration of CHS-Na. 2. The metabolism of CHS-Na was investigated in rabbits pretreated with cyclo-hexylamine, cyclohexanone, or cyclohexanol and the urinary excretion of CHS-Na metabolites increased in the animals pretreated with cyclohexylamine or cyclohexanone. 3. The produced amounts of CHS-Na metabolites increased in the liver of CHS-Na-treated rabbit and scarcely changed in the liver of CHS-Na-treated rat. 4. The metabolism of cyclohexylamine showed an increase of urinary excretion of cyclohexylamine metabolites in rabbit and rat following prolonged administration of cyclohexylamine. On the other hand, the in vitro metabolism of cyclohexylamine resulted in an increase of cyclohexylamine metabolites in the liver of the cyclohexylaminetreated rabbit and did not show a conspicuous difference between the livers of control and the cyclohexylamine-treated rats. 5. These results demonstrated that prolonged administration of CHS-Na caused a stimulation of rabbit liver enzymes metabolizing CHS-Na and potentiated a certain process degrating CHS-Na in rat gut.

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Oral administration of 2-aminoethianethiosulfuric acid offered a powerful protective action in mice against X-radiation of 600-800R. The effectiveness continued for more than 6hr after ingestion of the compound. The radiation protective. effect of the compound was not observed, however, in the animals which received 900RR radiation. S-Sulfocysteine was also radioprotective orally, but the effectiveness faded away in one hr.

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To investigate the metabolic fate of cefazolin (CEZ), a new semisynthetic cephalosporin analogue, two kinds of ¹⁴C-labeled CEZ were synthesized. The distribution of ¹⁴C-labeled CEZ in rats and mice after parenteral administration was studied using whole body autoradiography and liquid scintillation counting. The results of both studies agreed well in many aspects. Very rapid distribution throughout the whole body, except for the brain and fetuses, and complete elimination of the radioactivity in a short term were observed.

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Flavor enhancing activities synergistic with monosodium L-glutamate and stimulus thresholds of ribonucleotide derivatives have been correlated with their chemical structures following Hansch-Fujita's method. Regression analyses were made separately for two groups, 2-substituted inosine 5'-phosphates and S-substituted 2-mercaptoinosine 5'-phosphates. Superdelocalizability, net π-charge, Hammett σ_m, and hydrophobic parameter π were used in the analyses. Nuclear magnetic resonance chemical shift of the-SCH₂X group and a dummy variable D, which represents a proton accepting oxygen atom at the γ- or δ-position from the sulfur atom in substituents attached to the 2-position of purine skeleton, were employed successfully in a series of 2-S-substituted derivatives. In a series of 2-substituted derivatives, it has been recognized that flavor enhancing activities are influenced by Hammett σm and electrophilic superdelocalizability at the α-position of substituents (S_2a), whereas thresholds are correlated with S_2a and π. In a series of 2-S-substituted derivatives, it has been shown that π, D, and electrophilic superdelocalizability of the methylene protons in the -CH₂S-group of substituents play important roles in the structure-activity relationships.

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Thirty one 2, 6-disubstituted-trans-decalins were chromatographed on carbowax 20M and OV-1 columns, and the retention volumes were converted into the Kovats' retention indices. The increments of some substituents (OH, OCH₃, Cl, OAc, CN, COOCH₃, C₆H₅) were determined on the basis of the additivity rule. Elution characteristics of the investigated stereoisomers were reported and discussed.

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Disappearance of nitrofuran derivatives in pH 7.0 culture media and in the media inoculated with Staphylococcus aureus was investigated at 37°. From the media inoculated with the bacteria, rapid disappearance which followed a biexponential profile was observed in contrast to the monoexponential one observed with the media excluding the bacteria. Apparent rate of disappearance was dependent on the bacterial contents, concentration of the drugs. and the compositions of the media. Generally, vinyl derivatives were more susceptible to the process than azomethine ones. Equilibrium dialysis behavior, extent of the binding of the drugs to the crude membrane fraction of the bacteria, and the effect of medium compositions on the disappearance as well as the binding tendency of the drugs together with the inhibitory effect of p-chloromercurybenzoate suggest the possible involvement of a specialized transport process in the disappearance of nitrofurans from the culture media inoculated with the bacteria. The implications of these results from in vitro biological activity standpoint are discussed.

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Acute effect of EDTA-2Na, tetracycline-HCl, and Sodium laurylsulfate on the permeability of the rat small intestine was examined histologically using light microscope and scanning electron microscope. Specimens were obtained from the proximal small intestine after recirculation of the physiological buffer solution of the test compounds through the entire rat small intestine. It was observed that although the remarkable facilitating effect in the absorption of otherwise poorly absobable compounds reported in the literature was common, histological changes were different each other.

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Effects of the pretreatment with phenobarbital or 3-methylcholanthrene on the hydroxylase activity of rats liver microsomes were examined with 3-deoxyestrone. The administration of phenobarbital stimulated the 6β-hydroxylase, while the 3-methyl-cholanthrene treatment increased the rate of aromatic hydroxylation selectively. The biotransformation products formed from 3-deoxyestrone with the hepatic microsomes could be characterized by the reverse isotope dilution method and the chromatographic behaviors.

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A cytotoxic agent which inhibits the division of HeLa cells at metaphase stage was isolated from Thujopsis dolabrata (L. fil.) SIEB. et ZUCC. and identified as desoxypodophyllotoxin. Three substances, desoxypodophillic acid, desoxypicropodophyllin and β-peltatin-B-methylether were isolated from the recrystallization mother liquor of desoxypodophyllotoxin after treatment with alkali. Desoxypodophyllotoxin was found to be almost exclusively contained in the leaf and bark of this tree and only in minute quantity in its wood. It was also shown to be contained in T. dolabrata var. hondae MAKINO, Juniperus rigida SIEB. et ZUCC. and J. chinensis L. by thin-layer chromatography and cytotoxicity.

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Catalytic hydrogenolyses of the benzylidene compounds, in which two oxygens, two nitrogens and both oxygen and nitrogen are bound to the α-carbon of the benzylidene, were investigated in order to know the condition of hydrogenolysis, which may affect one of the two bonds, if possible, and either one of the two when the two are different. Partial hydrogenolyses of the N, N'-benzylidenediamines and O, O'-benzylidenediethers and selective hydrogenolyses of the α-alkoxybenzylamines and N-(α-aminobenzyl) amides were realized by the method of using palladium-on-charcoal and Raney nickel catalyst. The catalytic hydrogenolyses of the latter two were influenced by solvent used and were selectively effected at the carbon-oxygen bond of the α-alkoxybenzylamines and at the carbon-amine nitrogen or carbon-amide nitrogen bond of the N-(α-aminobenzyl) amides.

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On irradiation of N-chloroacetyl derivatives of 3-methoxyphenethylamine (VII) and 3, 5-dimethoxyphenethylamine (XV) in 10% aqueous ethanol, 1, 2, 4, 5-tetrahydro-3H-3-benzazepin-2-ones (VIII, IX, and XVI) were synthesized in good yield, whereas in ethanol novel ten-membered lactams (XIII and XVII) were main products. The photo-reaction of N-chloroacetylphenethylamine (XXI) in the presence or absence of veratrol (XXV) gave the intermolecular reaction product (XXVI) or the radical reaction products (XXII and XXIV), which may support the proposed dualistic mechanism.

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Hexosamine content of pyloric tissue of the stomach in rats exposed to fasting, water immersion and restraint stress, and cortisone treatment was determined. Water immersion and restraint stress, and cortisone treatment resulted in the decreased hexosamine content. Anti-ulcer drugs were administered to these animals orally. In the water immersion and restraint stress the hexosamine content of pyloric tissue of the rats was increased by tyrosine, threonine, glutamine, gefarnate, synthetic aluminum silicate and sodium copper chlorophylline. Glutamine, gefarnate and sodium copper chlorophylline also induced the increase in hexosamine content of the rat pyloric tissue treated with cortisone acetate.

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An antitumor active aqueous extract was obtained from P. ostreatus (Fr.) QUEL. The fractionation by ethanol precipitation, ultrafiltration with molecular sieve membrane and adsorption on DEAE-Sephadex were effective to purify an antitumor active fraction A₅ as one spot on a electrophoresis, and to isolate another active fraction A₃ and an inactive fraction A₆. The active fraction A₅ and A₃ were constituted of macromolecular polysaccharide, but molecular size of the inactive fraction A₆ was smaller than those of the active fractions. The main component sugar was glucose in the fraction A₅ and A₃, but it was galactose in the fraction A₆. The fraction A₅ differed from the fraction A₃ in a point of including acidic sugar.

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The structure of the fluorescent compound (A) obtained from the reaction of dulcin and sodium nitrite was previously presumed to be 1, 3-bis (4-ethoxyphenyl)-5-tetrazolone. In this paper, (2-bromoethoxy) phenyl derivative (B) which has the same structural skeleton of compound A was synthesized and analized by the single crystal X-ray diffraction method to determine the structure more conclusively. The structure of compound B was discussed on the basis of the result of the two-dimensional analysis. The structure of the fluorescent compound A was consequently concluded as 1, 3-bis (4-ethoxyphenyl)-5-tetrazolone.

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Various compounds related to the hypocholesterolemic alkaloid eritadenine (I) were synthesized for the evaluation of structure-activity relationships in this series. 6-Sub-stituted purine analogs were prepared by reacting the 6-chloro-purine intermediate (II) with the corresponding nucleophilic reagents. 2, 6-Di-substituted purine derivatives were prepared by utilizing a route involving an imidazole ring closure step, starting from the appropriately substituted pyrimidine precursors and the amino-acid (VI). The preparation of 6, 8-di-substituted purine analogs was achieved by cyclization of the 5-amino-pyrimidine intermediate (XXIX) derived for the synthesis of I.

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The chemical structures of nivalenol, fusarenon-X and diacetylnivalenol, toxic principles produced by Fusarium nivale Fn-2-B, have been confirmed as 3α, 4β, 7α, 15-tetra-hydroxy-scirp-9-en-8-one, 3α, 7α, 15-trihydroxy-4β-acetoxy-scirp-9-en-8-one and 3α, 7α-dihydroxy-4β, 15-diacetoxy-scirp-9-en-8-one respectively by the interconnection with the scirpene type compounds and their physico-chemical properties. The some aspects with respect to ketoform and non-keto-form on C-8-carbonyl of nivalenol were described. The mass spectrometric fragmentation processes of nivalenol and its derivatives were also described.

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On acid treatments, betulafolianetriol (VII) having the same configuration at C₍₂₀₎ as dammarenediol II (VI) gave an equilibrated mixture of VII and its C₍₂₀₎ epimer (VIII). The derivatives of betulafolienetriol (IV) and VII having a hydroxyl or methoxyl group at C₍₁₂₎ also showed the configurational equilibration at C₍₂₀₎ hydroxyl under the same condition, whereas those without hydroxyl or methoxyl at C₍₁₂₎ showed no or negligible epimerization at C₍₂₀₎. The acid catalyzed pyran ring formation from the side chain of betulafolienetriol (IV) gave 3, 20-epi-panaxadiol (XII) and 3-epi-panaxadiol (XI) by the retention and the inversion of its C₍₂₀₎-configuration, respectively. It reveals that C₍₂₀₎-configuration of panaxadiol (I) and protopanaxadiol (III) (epimeric at C₍₃₎ and C₍₂₀₎ of IV) are same as that of dammarenediol I (V). Since the chirality at C₍₂₀₎ of panaxadiol (I) has already been established as R, dammarenediol I type triterpenes have (R)-configuration at C₍₂₀₎, and dammarenediol II type compounds S. This conclusion has also been supported by the IR-absorptions of C₍₂₀₎ keto and C₍₂₀₎ hydroxyl of 12-keto-3-acetates (XVII and XVIII) of betulafolianetriol (VII) and dihydroprotopanaxadiol (X). The mechanism of epimerization at C₍₂₀₎ on the acid treatments of dammaran-20-olcompounds having O-function at C₍₁₂₎ was discussed.

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The sapogenin of Ginseng saponins, ginsenosides-Rb₁, -Rb₂ and -Rc, was once reported to be protopanaxadiol (III). But it was found recently that dammarane type triperpenes with hydroxyl or methoxyl group at C₍₁₂₎ and C₍₂₀₎ give an equilibrated mixture of epimeric compounds at C₍₂₀₎. On mild hydrolysis of the saponins 20-epi-protopanaxadiol has been obtained as the genuine sapogenin for which the name of 20 (S)-protopanaxadiol (V) is proposed. The prosapogenin (XI), which was obtained by the partial hydrolysis of the above mentioned three saponins is found to be 3-O-(2β-D-glucopyranosyl-β-D-glucopyranosyl)-20 (R)-protopanaxadiol. The remaining glycosidic linkage in ginsenosides-Rb₁, -Rb₂ and -Rc should be located at C₍₂₀₎-OH.

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In order to study the structure-reactivity relationship in the intramolecular catalyzed hydrolysis of amide, a series of aliphatic hydroxyamides was subjected to acid-catalyzed hydrolysis. Paper chromatogram verified that the hydroxyamides, which had high rates compared with those of the corresponding alkyl analogues, produced the corresponding lactones in their hydrolytic processes. Their reaction pathways were classified theoretically into three schema. The Arrhenius parameters of entropy and enthalpy or activation were determined and the mechanisms of lactonization and hydroxy acid formation were discussed from entropy-enthalpy relationship. The proposed mechanisms were supported by the appropriate kinetic data.

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The pyrolysis of tetrahydrodesoxyusnic-and dihydrousnic acids and their acetates was studied and the reaction mechanisms were proposed.

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The sapogenol constituents of two Theaceous plant materials : seeds of Camellia sasanqua THUNB. and leaves of Ternstroemia japonica THUNB., have been examined in connection with the previous investigation on tea seeds sapogenols. In addition to eight known oleanane triterpenoids : dihydropriverogenin A (II), camelliagenin B (III), A₁-barrigenol (IV), camelliagenin C (V), barringtogenol C (VI), camelliagenin D (VII), theasapogenol E (VIII), and theasapogenol A (IX), a new sapogenol designated as 22α-hydroxy-erythrodiol (I) has been isolated from the former seeds while oleanolic acid, primulagenin A (XIV), dihydropriverogenin A, and A₁-barrigenol have been obtained from the latter leaves. Isolation of primulagenin A from the Theaceous plant material seems to be unprecedented.

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Isolation and characterization of metabolites of furazabol (17β-hydroxy-17α-methyl-5α-androstano [2, 3-c] furazan; IIa) following oral or subcutaneous administration of the compound to rats are described. From faeces were obtained the corresponding 18, 17β-lactone (I), unchanged furazabol, the 16β-hydroxylated compound (III), the 18-hydroxy-lated compound (IV), the 17α-hydroxymethyl derivative (V), the 18-carboxylic acid (VII) and a compound assumed to be the 4β, 16ξ-dihydroxylated 18, 17β-lactone (VI). In the bile the lactone (I) and probably the conjugated metabolites were present. Urinary metabolites were not characterized. The furazan ring of furazabol appeared to be stable in vivo. The metabolic significance of the isolated compounds is discussed.

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The compounds required for the study of the metabolites of furazabol (17β-hydroxy-17α-methyl-5α-androstano [2, 3-c] furazan ; Ia) were synthesized ; these are the labelled furazabol (Ib) with ¹⁴C at 17α-methyl position, the 18-hydroxy derivative (II) of furazabol, the 18, 17β-lactone (III), 18-oic acid (IVa), the 16β-hydroxy derivative (Va) and the 17α-hydroxymethyl derivative (VIa). Oxidation of the 18, 17β-dihydroxy-17α-methyl compound (II) with chromic acid proved to give the corresponding 18, 17β-lactone (III) and 18-oic acid (IVa).

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Detailed examinations on nitrous acid deaminations of L-phenylalanine ethyl ester (Ib) and its p-nitro (Ia) and p-methoxy (Ic) derivatives in 1 N sulfuric acid, acetic acid, and trifluoroacetic acid have shown that the reactions are highly dependent both on the solvent employed and on the substituent attached to the aromatic ring. Results may be rationalized by evaluating the changes in nucleophilicities of both the solvent and the aryl group. We clearly demonstrated that aryl groups exhibit strong neighboring group participation in deamination in trifluoroacetic acid.

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Detailed examinations of nitrous acid deaminations of L-phenylalanine (VIb) and its p-nitro (VIa) and p-methoxy (VIc) derivatives in 1 N sulfuric acid, acetic acid, and trifluoroacetic acid have shown that the reaction patterns (yields of products and their stereochemical results) differ considerably both with the solvent employed and with the substituent attached to the aromatic ring. These results were explained as due to effects of both the neighboring carboxylate group and the neighboring aryl group. Successful conversion of L-phenylalanine to naturally occurring (S)-tropic acid ((S)-VIIIb X=OH) is also described by the application of the present results.

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Administration experiments of labelled compounds into several plants revealed that 7-desoxyloganic acid is the intermediate in the biosynthesis of iridoid glucosides such as verbenalin (2), loganin (4), geniposide (5), asperuloside (6), and aucubin (10). Tracer experiments on asperuloside (6) proved that loganin (4) (or loganic acid (3)) locates biosynthetically between 7-desoxyloganic acid (1) and the glucosides formed after geniposide (5).

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Oxidation reaction of d-δ-tocopherol (I) and δ-tocopherol model compound (II) are carried out with silver nitrate as oxidizing agent in ethyl alcohol. Three novel oxidation products are isolated and characterized. They are atropisomers of (+)-5-(δ-tocopherol-5'-yl)-δ-tocopherol (VII, with R-configuration at C₅-C_5' position, IX with S-configuration at C₅-C_5' position), and 5-(6'-hydroxy-2', 2', 8'-trimethylchroman-5'-yl)-6-hydroxy-2, 2, 8-trimethylchroman (XI).

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The oxidative sequences for the formation of several iridoid glucosides from 7-desoxy-loganic acid via loganic acid have been established.

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Potato-kallikrein-inhibitors (PKI) showed the anti-inflammatory potency in rat carrageenin edema and reduced the exudation of leucocytes into carboxymethylcellulose pouch in the dorsum of rats, but not the protein exudation. PKI was not effective against egg white edema, which was depressed by α-chymotrypsin to some extent. PKI showed the inhibitory action on the release of vasodilative substances produced from rat serum (pH 4) and human plasma (pH 5) by acidification in vitro, which might be the products (kinin- and kallikrein-like, respectively) from the activation of kallikreinkinin system. PKI also inhibited the acetone activation of human plasma. These inhibitory actions of PKI were stronger than Trasylol using equal kallikrein inhibitor units. In the rat anaphylactic shock provoked by challenging with horse serum as antigen, PKI, Trasylol, soybean trypsin inhibitor and other tested substances for the inhibition of anaphylaxis did not show the definite effectiveness on the survival rate of rats.

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