The correlation between the chromodacryorrhea and the excess porphyrin formation by the Harderian gland of pantothenic acid-deficient rat was examined. It was thereby found that the main porphyrin in the red tears on pantothenic acid-deficient rats was not coproporphyrin, reported by McElroy, et al., but was protoporphyrin-IX, thin-layer chromatographycally and spectrophotometrically. According to the measurement of porphyrin content and δ-aminolevulinic acid synthetase (succinyl-CoA : glycine C-succinyl-transferase (decarboxylating), EC 2.3.1.37) activity in the Harderian gland, it was assumed that the chromodacryorrhea was caused by secretion of excess protoporphyrin formed due to the increase in δ-aminolevulinic acid synthetase activity and the hypertrophy of Harderian gland.

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Regression analyses using the Free-Wilson technique were applied to the anti-inflam-matory effect and the acute toxicity of 57 1, 3, 5-trisubstituted 2, 4, 6-trioxoperhydropyrimidine derivatives. Models for the orientation of substituents on the "receptor site" are presented. A significant correlation was obtained by assuming that one of the N-substituents with a high hydrophobicity always locates at a particular binding site. Further analysis of the contributions of substituents at the 5-position using the free energy related hydrophobic parameter, π revealed that acute toxicity increases with an increase in the hydrophobicity of the 5-substituents. 1-Cyclohexyl-5-butyl or -allyl derivatives seemed to be the most suitable anti-inflammatory agents in terms of their high activity and low toxicity.

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The transamination reaction of thiazole moiety of thiamine (PyTh) by aromatic amine (A) in the presence of bisulfite (S) was studied kinetically. The reaction between PyTh and A was found to be second order with respect to PyTh and A, whereas the concentration of S was independent to the reaction rate. The reaction rate was linearly correlated to the pK_a value of A. The transamination product (PyA) was also degradated by S in second order as well as PyTh. The complexation between PyTh and A was also investigated as a possible proceeding process of the transamination reaction.

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The stereostructures of pyranocoumarin derivatives named decursin (I), decursidin (II), AD-I (III), AD-II (IV) isolated from the root of the titled plant have been elucidated on the basis of chemical and physicochemical evidence. Decursin is expressed as 3'(S)-senecioyloxy-3', 4'-dihydroxanthyletin (I) and decursidin as -3'(S), 4'(R)-disenecioyloxy-3', 4'-dihydroxanthyletin (II). AD-I has been revealed to be a mixture of two diastereoisomers being isomeric at C-4' and is expressed as 3'(S)-angeloyloxy-4'(R and S)-isovaleroyloxy-3', 4'-dihydroxanthyletin (III). Finally, AD-II has been established to be -3'(S)-angeloyloxy- 4'(R)-senecioyloxy-3', 4'-dihydroxanthyletin (IV) and it has been suggested on the basis of close similarity of the physical properties of AD-II with those of andelin that the structure proposed for andelin by Avramenko, et al. might be revised.

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The acid dissociation constants of hydroxyphenazine derivatives having the oxine-like functional group and the formation constants of their metal chelates with cobalt [II], nickel [II], copper [II], zinc [II] and cadmium [II] were measured in a 50% (v/v) ethanol solution at 25±1° by the spectrophotometry. Considering from the formation constants of Ni- and Zn-chelates, it was found that the metal chelates of hydroxyphenazine derivatives indicated the similar steric hindrance to those of the 2-substituted oxine metal chelates.

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5-Chlorouridine (III), 5-chlorocytidine (IV), and 5-chloro-1-β-D-arabinofuranosylcytosine (VIII) were obtained in a yield of 61%, 61%, and 11.2% respectively by reaction of pyrimidine nucleosides with N-chlorosuccinimide. 2, 2'-Anhydro-5-chloro-1-β-D-arabinofuranosyl cytosine (XI) was prepared in a yield of 53% by reaction of IV with Vilsmeier-Haack reagent. 5-Chloropyrimidine nucleosides (III, 5-chloro-1-β-D-arabinofuranosyluracil (VII), IV, and VIII) were found to degrade in aqueous alkali (1 N NaOH) at 50° via deamination or 6, 2' (or 5')-anhydro open-chain ureido compounds. IV was more readily degraded in 0.3 N KOH at 37° than non-chlorinated (II). An unique reaction was that the treatment of XI with 0.1 N NaOH at room temperature afforded 2, 2'-anhydro-5-hydroxy-1-β-D-arabinofuranosylcytosine (XII) without splitting the anhydro bond.

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The effects of various surfactants on the intramuscular absorption of water-soluble, micelle-free drug was studied using isonicotinamide as a model compound. 1) Lineality of the clearance curves of the drug was kept even in the presence of either nonionic or ionic surfactants, which indicates that the fundamental mechanism of absorption was unaltered. 2) Absorption inhibitory effects were not specific to nonionic surfactants but were also found in ionic ones in almost equal degrees, and concentration dependency as well. 3) In regard to the homologous serics of polyoxyethylene derivatives of hydrogenated castor oil (HCOs), it has been observed that the smaller the molecular weight and the hydrophlie lipophlie balance are, the greater is the inhibitory effect.

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2-Ethylthiothiazoline was reacted with N-benzoyl-α-amino acids in acetic anhydride to give I. Ia was converted into II, III, IV, and V. The oxazolone ring of Ib and Ic was opened to give XI. XIb was converted into thiazoline (XII) and XIII. These thiazolines were reduced to thiazolidine (XIV) and XV, and then converted into the respective aldehydes, XVI and XVII.

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The rates of the Dimroth rearrangements of 1-alkyladenosines (Ie, f) and 1-alkyl-9-methyladenines (Ia-d) at various pH's and ionic strength 1.0 at 40° have been measured. It has been shown that all reactions obey good pseudo-first-order kinetics and follow the rate law given by k⁽⁰⁾_obsd=k⁽⁰⁾_ionic [I·H⁺] [OH^-]+k⁽⁰⁾_neut [I] [OH^-] where k⁽⁰⁾_obsd is the observed limiting specific rate for zero buffer concentration ; [I·H⁺] is the fraction of the base protonated at each pH ; [I], the fraction present as free base. Comparison between the individual second-order rate constants thus obtained (Table III) has revealed that attack of hydroxide ion on the protonated species is faster than on the neutral species by a factor of 90-1100 and that the former is affected by the electronic property of a substituent at the 1-position, whereas the latter is influenced by a steric factor. The rate of the rearrangement is enhanced by the benzyl group at the 1-position at near neutrality and by the β-D-ribofuranosyl group at the 9-position at all pH's examined.

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2-(2-Hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic acid (HQ II), as an analogue of 2-(2-hydroxyphenyliminomethyl)-4-n-hexylphenol (HP) which exhibits anticancer activity, was prepared by the method of Doebner synthesis. HQ II, having the ability to form metal complexes with several metallic ions as well as HP, inhibited prominently the growth of Ehrlich ascites carcinoma and ascites hepatoma AH 13 in animals. However, it was not effective against L1210, solid tumors of both Sarcoma 180 and Ehrlich carcinoma and Yoshida sarcoma. From the results of preliminary examinations which were carried out to obtain some information concerning the mode of action of HQ II on cancer cells, it was suggested that the cell membrane injury and the inhibition of nucleic acid synthesis might be contributable to the HQ II effect on the susceptive cancer cells.

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The mode of action of 2-(2-hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic acid (HQ II) was studied using mainly ascites hepatoma AH 13 (AH 13) cells in culture. 1) In vitro, HQ II causes hemolysis of rabbit erythrocytes and injures cancer cells. However, these effects are not appeared in the medium containing some amounts of serum. 2) Even in the culture containing serum, HQ II inhibits the proliferation of AH 13 cells and causes selective inhibition of desoxyribonucleic acid (DNA) synthesis. These actions are mostly restored by washing or addition of Fe salts. 3) Uptake of ³H-thymidine, ³H-deoxycytidine (³H-CdR), and ³H-cytidine (³H-CR) to the cellular acid-solubles are not decreased by HQ II treatment. However, the incorporations to DNA in turn are prominently inhibited. 4) The conversion of ³H-CR to ³H-CdR nucleotides is inhibited in the cells treated with HQ II. 5) The exogenous addition of a certain composition of deoxyribonucleosides to the medium can suppress the inhibitory effect of HQ II on DNA synthesis. 6) The reduction of ¹⁴C-CR diphosphate to ¹⁴C-CdR nucleotides in cell-free extracts of AH 13 cells is prominently inhibited by the agent. HQ II causes the cell membrane injury and/or inhibits selectively DNA synthesis in AH 13 cells. The results suggest that the inhibition of DNA synthesis caused by HQ II having metal-chelate-forming ability may be due to the interaction of the agent with the extracellular and/or intracellular Fe (in which ribonucleotide reductase may be involved.).

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Reaction of dimethyloxosulfonium-(I), dimethylsulfonium-(II), and tetramethylenesulfonium benzoylmethylide (III) with 2, 2-diacetyl- and 2-acetyl-2-ethoxycarbonyl-1-ethoxyethylene (VI), in the presence of triethylamine afforded the corresponding 1-benzoyl-3, 3-diacetyl- and -3-acetyl-3-ethoxycarbonylallylides (VII, VIII, and IX) in a good yield. Similar treatment of ethoxycarbonylmethyldimethyl- and ethoxycarbonyltetramethylene sulfonium bromides (IV and V) with VI gave the corresponding allylides (X and XI). These 3, 3-diacetylallylides (VII and VIII) and 3-acetyl-3-ethoxycarbonylallylides (X) were hydrolyzed to the corresponding 3-acetylallylides (XII, XIII, and XIV) by treatment with dilute hydrochloric acid under a mild condition.

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The decomposition of acetylsalicylic acid (I), acetyl-5-nitrosalicylic acid (II) and acetyl-5-chlorosalicylic acid (III) in solid state by water vapor were studied for an approach to elucidate the decomposition mechanisms of organic crystals by water vapor. All three materials showed the sigmoid-type decomposition curves and the order of the intensity of acceleration at early stage was II>III>I. From the decomposition study of pre-decomposed I and II, it was revealed that the accumulation of formed salicylic acids and/or acetic were not the cause of acceleration. Microscopic observation of advancement of reaction about II showed that the reaction starts partially on the crystals and then spread over all the crystals. It was concluded that the acceleration is attributed to the formation and growth of reaction nucleus as its wider sense. The decomposition curves were anaylzed by the empirical equation (dX/dt=(1-X)^m×k^l+1×t^l), where X, t, and k are the decomposition fraction, decomposition time, and the apparent decomposition rate constant, respectively, and where m and l are parameters. The apparent activation energies of decomposition of three materials were 30 kcal/mol, and the k of II linearly increases as the relative humidity rises.

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The reactions of 1, 3-glycol monotosylates of the configurations A-D with base and LAH were discussed. On reaction with t-butoxide, A and D (cis relationship between-OH and -CH₂OTs) gave oxetanes E and F respectively, while B and C (trans relationship between these groups) gave the same seco-aldehyde G. On LAH reduction, in addition to the above reaction (oxetane formation from A and D, seco-alcohol formation from B and C), two further reactions took place ; a) S-O fission (formation of the glycols A-D), and b) C-O fission (formation of the deoxy-compounds H and I), for the latter reaction the cyclic intermediate (K-M) were proposed. The monotosylate of B did not give deoxy-compound. The corresponding keto-tosylate (N and O), when treated with lithium aluminum hydride firstly gave 3β-alcohols (A and C) which are further reduced as above ; the fact which therefore opened a way to yield deoxy-compound (I) from type B glycol (B→N→I).

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The absorption spectra of salicylamine (ο-hydroxybenzylamine) (I), thiosalicylamine (ο-mercaptobenzylamine) (II), and 3-hydroxy-4-aminomethylpyridine (III), have been measured at various concentrations of added acid or alkali in methanol solution. Assignments of the absorption bands to the various molecular species are made. I existed as a nonpolar species, whereas II did as a dipolar species with a dissociated thiol group, in neutral methanol solutions. This was supported by the pKa values (I ; 9.2, 10.5 : II ; 4.7, 9.5) calculated from potentiometric titration curves in aqueous solutions. Both polar and nonpolar species were present in a neutral methanol solution of III. The Al [III], Cd [II], Ni [II] and Zn [II] chelates of II were fairly stable, whereas those of I were not formed appreciably, in methanol. III formed Al [III], Cd [II], Cu [II], Ni [II], and Zn [II] chelates, spectra of which were quite similar to those of metal chelates of pyridoxamine. Spectral change of a solution containing II and Cu [II] ion shows II formed Cu [II] chelate and, then, was converted to benzisothiazol. In the presence of Zn [II] ion, II and sodium pyruvate formed Zn [II] chelate of ketimine Schiff base, which underwent tautomerization to that of aldimine Schiff base very slowly. Possible correlation is noted between pKa's of the phenolic group of pyridoxamine and its analogs and their abilities to form metal chelates and to catalyze the nonenzymatic transamination.

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Structure of stepinonine (1a), isolated from Stephania japonica MIERS grown in Formosa, was established through the reductive fission (Chart 2) of N, O-dimethyltetrahydrostepinonine (4) with sodium in liquid ammonia, oxidation of O-ethyl-N-methyltetrahydrostepinonine (16) with KMnO₄ (Chart 5), and the reductive fission of the deuterated product (18) derived from stepinonine (Chart 6). Syntheses of the 3-benzazepine derivatives, (15 a, b, c) and mass spectrometric fragmentation of these compounds were also presented.

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The natural-abundance ¹³C nuclear magnetic resonance spectra of certain phytoecdysones and their selected derivatives have been measured at 25 MHz. With the aid of complete noise, off-resonance, and single-frequency proton decoupling techniques, and the shifts which occur on formation of specific derivatives, it has been possible to make assignments of the resonances for the phytoecdysones.

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Stepinonine (1) was chemically converted to O-methylrepandine (2) and O-methyloxyacanthine (3) via N, O-dimethyltetrahydrostepinonine (17) which was subjected to oxidation with Jones' reagent, followed by reduction with Zn-AcOH and NaBH₄.

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Structures of two new polyoxypregnane ester-type aglycones ; 12-O-cinnamoyl-20-O-ikemaoylsarcostin (VII) and 12-O-cinnamoyl-20-O-tigloylsarcostin (VIII), from the glycoside of C. wilfordi HEMSLEY, were elucidated by chemical and physicochemical analyses. Kidjoranin (IV), caudatin (V) and penupogenin (VI) were also obtained.

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Quaternization of benzo [a] quinolizidine (Ib) with methyl iodide gave a 3.6 : 1 mixture of the cis- (IIb : X=I) and the trans-methiodide (IIIb : X=I). The 9, 10-dimethoxy derivative (Ia) also gave the corresponding cis- (IIa : X=I) and trans-methiodide (IIIa : X=I) in a ratio of 3.3 to 1. Treatment of enamines Va, b with methyl iodide furnished the N-methylated product (VIa, b) and the C-methylated product (VIIa, b) in a ratio of 1.2 : 1. Catalytic hydrogenation of VIa, b produced a mixture of the cis- (IIa, b) and the trans-methosalt (IIIa, b) in a rough ratio of 2.8 : 1, whereas that of VIIa, b gave the 1-methylated benzo [a] quinolizidine (VIIIa, b). Compound VIIIa was alternatively prepared from piperidone IX by the Bischler-Napieralski cyclization and subsequent hydrogenation. In the case of the simple quinolizidine system with the simplest β, γ-unsaturation (XV), the quaternization with methyl iodide produced the cis- (XVI) and the trans-methiodide (XVII) almost equally. Repetition of the known methiodide formation of XXVI and hydrogenation of enamine methiodide XIX confirmed their reported high stereoselectivity, and factors responsible for the difference in stereoselectivity between these reactions of the β, γ-unsaturated system and the saturated system have been discussed. At 250° the cis-methiodides (IIa, b, XX) isomerized to the corresponding trans-fused salts (IIIa, b, XXI) to some extent and one may roughly compare the susceptibilities of IIa, IIb, and XX, which decrease in that order.

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Major water-soluble extracellular polysaccharide C. tricoides obtained by diethylaminoethyl-cellulose column fractionation is a heteroglycan, [α]³⁰_D-34° (c=1, H₂O), which was composed of D-galactose, D-glucose, D-mannose, and L-rhamnose (7.3 : 1.0 : 8.7 : 2.2). The results of periodate oxidation, Smith-type degradation, methylation studies, and GC-mass spectra showed that the polysaccharide has a highly branched structure and contains 1→6 linked mannopyranosyl, 1→4 linked galactopyranosyl and 1→2 linked galactofuranosyl residues as main units, and that the glycan is branched at C2 and C3 or C6 positions of mannose residue. The terminal groups are rhamnopyranosyl, galactofuranosyl, and mannopyranosyl residues. A probable structure was proposed.

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An antigenic lipopolysaccharide, serratigen isolated from Serratia marcescens was mainly made up of galactose and contained 18.4% of galacturonic acid. It had α-(1→3) galactan moiety in the molecule. The chemical structure of serratimannan isolated from the same strain was shown to have α-(1→2) and α-(1→3) linkages in mannan.

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Amination of α-lithiated carboxylic acid salts was investigated using isovaleric acid mainly. Methoxyamine bearing a proper electronic character was the best aminating reagent, as shown in Table I. Several α-amino acids, e.g., valine, leucine, methionine, phenylalanine, and α-phenylglycine, were prepared by this new method, summarized in Table II. The synthesis of two new aminating reagents, 3, 5-dinitromesitoxyamine and 2-tetrahydropyranyloxyamine were described.

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N, N-Diethyl phenylacetamide and N-n-butyl phenylacetamide were respectively α-lithiated, followed by amination with methoxyamine to give α-phenylglycine N, N-diethylamide (IVa) and α-phenylglycine N-n-butylamide (IVc). However, phenylacetamide gave phenylglyoxylamide only and tert-butyl phenylacetate did not undergo the above amination reaction. Benzylisocyanide and N-(diphenylmethylene) benzylamine (VII) were respectively α-lithiated, subjected to carboxylation, followed by acid hydrolysis to give α-phenylglycine (I) in good yields.

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In order to investigate the transfer of ampicillin and pivampicillin in biological systems, the sensitive separatory determination method of ampicillin and aminobenzyl-penicilloic acid in presence of pivampicillin was developed. This method is based on the separation of these substances utilizing their different distribution behavior between the aqueous phase and the chloroform phase, followed by fluorometric determination. In the transfered studies in biological systems, marked differences were found in the rate of absorption and the amount of excretion between ampicillin and pivampicillin. Biotrans-formational studies were also discussed.

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The present paper provides a new useful means of synthesis of 2, 3, 3-trisubstituted phthalimidines. Alkylation of phthalimidines at 3-position has been found to proceed with alkyl halide in liquid ammonia in the presence of potassium amide.

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The interaction of tranquilizing drugs phenothiazines with β-cyclodextrin in aqueous solution was studied by circular dichroism, ultraviolet (UV) absorption, and proton magnetic resonance spectroscopies. The induced circular dichroism bands and UV absorption changes were quantitatively investigated and stoichiometric ratio, which was found to be 1 : 1, and formation constants of inclusion complexes were obtained. In β-cyclodextrin-drug system, protons located in a cavity of β-cyclodextrin were found to be subjected to anisotropic shielding, while protons of phenyl and N-substituted groups in the drug shifted to low field, in which all peaks caused remarkable broadening. Formation constants were correlated well with partition coefficient of drug and also with the magnitude of proton magnetic resonance spectral broadening. These spectral changes strongly suggested that aromatic portion of drug was included into hydrophobic cavity of β-cyclodextrin, while N-substituents of drug interacted with the outside groups of β-cyclodextrin cavity.

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Stereochemistry of the fluorination of an alcohol with phenyltetrafluorophosphorane was investigated in the case of steroidal alcohols. 5α-Cholestan-3β-ol and 3α-ol gave 3α- and 3β-fluoro-5α-cholestane, respectively, which suggests that the fluorination proceeded through SN2 mechanism ; while, cholesterol and 3β-acetoxy-5-bromo-5α-cholestane-6β-ol gave fluoro compounds with retention of configuration, which shows that a neighboring group may have participated in stabilizing the carbonium intermediate in special cases. Diphenyltrifluorophosphorane gave similar results.

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Inclusion of antiinflammatory drugs fenamates within the cavity of β-cyclodextrin in aqueous solution was confirmed by circular dichroism, ultraviolet absorption, and nuclear magnetic resonance spectroscopies. Solubility and spectral changes were quantitatively investigated and stoichiometric ratio, which was found to be 1 : 1, formation constants, and thermodvnamic parameters were obtained for complex formation of β-cyclodextrin with fenamates. Hydrophobic and steric factors were reflected in the values of formation constants. Isoequilibrium relationship between ΔH and ΔS values were observed having a compensation temperature of 284°K. From these evidences mode of inclusion was discussed.

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The ionic structures of mass fragments of mepirizole and its derivatives were studied with use of deuterium labelling technique, and the fragmentation processes were discussed. The structural elucidation of the metabolites based on their mass spectra is also described.

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The resolution of tryptophan, tyrosine and related compounds as their trimethyl-silylated N-trifluoroacetyl-L-prolyl amino acid n-butyl esters was studied by gas chromatography. It was found that tyrosine and 3, 4 dihydroxyphenylalanine were resolved, while α-methyl-3, 4 dihydroxyphenylalanine could not be resolved. The peaks of epinephrine, norepinephrine, metanephrine and normetanephrine, except for dopamine, were not observed. Tryptophan was not resolved completely.

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It has been found that N-(alkoxymethyl) dialkylamines and N, N'-methylenebisdialkylamines react with isocyanides, effecting 1, 1-addition by suffering split of one of the methylene carbon-heteroatom bonds. The reactions furnish the corresponding imidates and amidines as the products which are not otherwise obtainable.

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When N-methylmorpholine salt of Boc-Ile was coupled with HCl·Pro-Pro-resin suspended in methylenechloride by dicyclohexylcarbodiimide, diketopiperazine formation of the dipeptide-resin was suppressed almost completely and the isoleucine residue in the synthesized Boc-Ile-Pro-Pro-resin was not racemized. Generalization of this coupling procedure in a schedule for solid phase peptide synthesis is suggested.

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Tremendous activation of arginine esterases or trypsin-like enzymes from the dog pancreas was observed during DEAE-Sephadex A-50 chromatography of the pancreatic kallikrein. The esterase activity freshly assayed was 7.5 μmoles N^α-benzoyl-L-arginine ethyl ester (BAEE)/min per gram of the pancreas. The enzymes were separated into two fractions by Ampholine isoelectric focusing, their isoelectric points being 4.6 and 4.8. The two esterases purified showed the specific activities with 4.4-7.4 μmoles BAEE/min/A₂₈₀ and 20-36 μmoles N^α-p-toluenesulfonyl-L-arginine methyl ester (TAME)/min/A₂₈₀, and hydrolyzed N^α-benzoyl-DL-arginine-p-nitroanilide (BApNA) and casein. The esterases were strongly inhibited by Trasylol, soybean trypsin inhibitor, kallikrein inhibitors from potatoes, etc. From chemical and enzymatic properties, both esterases seemed to be anionic trypsins of the dog pancreas.

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A highly potent analog of luteinizing hormone releasing hormone (LH-RH), pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-NHCH₂-CH₃ was synthesized by the conventional solution method. The key intermediate, H-Leu-Arg (NO₂)-Pro-NHCH₂-CH₃, which was prepared by the stepwise manner using the activated esters of the corresponding protected amino acids, was coupled with N-terminal hexapeptide, pGlu-His-Trp-Ser-Tyr-Gly-OH, by the HONB/DCC method to give the mono-protected nonapeptide ethylamide. The protected peptide was treated with stannous chloride in 60% aqueous formic acid to remove the nitro group. The purification of the resulting peptide was carried out by a column chromatography on Amberlite XAD-2 and followed by a column chromatography on carboxymethylcellulose. The synthetic method described is promising for preparing this analog of LH-RH in large quantities and good quality.

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As a supplement of our program aimed at the synthesis and reaction of 1, 6-anhydro-6-deoxy-6-thio-β-mono- and di-saccharides, those of the corresponding derivative of 2-acylamino-2-deoxy-β-D-glucopyranose (acyl=acetyl or benzoyl) were described. Synthesis of 1, 6-anhydro-2-benzamido-2-deoxy-β-D-glucopyranose and acetolysis products of the diacetate were also reported.

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Excretion of creatinine into gastrointestinal tract was studied using renal-artery-ligated rats as a model of patients suffering from renal failure. In the rats of first group, both arterial branches of kidney and bile duct were ligated, and a saline solution was sent through the intestinal lumen to perform the intestinal dialysis. In the second group, after ligation of both renal arteries, a fine catheter was sutured with bile duct to collect the bile. After the intravenous administration of creatinine (138 mg or 34 mg/kg) through the femoral vein, the animals were kept for 1 hr until the creatinine level in body-fluid approach to steady state. Under these steady state conditions, about 170 μg or 70 μg of creatinine was permeated into gastrointestinal tract every 1 hr from upper and lower region of jejunal mucosa after the administration of 138 or 34 mg/kg of creatinine, respectively. The creatinine concentration in bile was similar to that in blood and about 200-270 μg or 90-110 μg of creatinine was excreted into bile every 1 hr after the injection of 138 or 34 mg/kg of creatinine, respectively. Creatinine excreted from the intestinal mucosa and bile was collected together by perfusing the saline solution for 3 hr. About 3.5% of creatinine was excreted. These results suggested that, at least, 20-30% of creatinine in body fluid may be excreted daily into gastrointestinal tract through the intestinal mucosa and from bile in the renal shutdown rats.

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Acid cholesterol esterase in the 9000 g precipitates of rat liver was stimulated by the addition of organophosphate pesticide, dimethyl dichlorovinyl phosphate (DDVP) in vitro. The major portion of the esterase in the 9000 g precipitates may be lysosomal esterase. The esterase activity was also stimulated by the osmotic treatment of the 9000 g precipitates as well as that in the presence of DDVP. However, the esterase activities in the osmotic treated-9000 g precipitates and the supernatant solution obtained by centrifugation after the osmotic treatment of the 9000 g precipitates were no longer stimulated by the addition of DDVP. These results suggest that the stimulatory effect of DDVP may be due to the release of the esterase by the disruption of lysosomal membrane or the translocation of the esterase on lysosomal membrane from a bound type a free one.

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S-Arylthiabenzene analogues were synthesized by the reactions between 2-thio-chromene 2-oxides and organometallic reagents such as aryllithiums and aryl Grignard reagents. The mechanism for the formation of the S-arylthiabenzene analogues was explained by postulating the formation of thiopyrylium ion as reaction intermediates.

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Bredinin, a novel imidazole nucleoside, produced by Eupenicillium brefeldianum M-2166 was synthesized by the condensation of the trimethylsilyl derivative of 4 (5)-carbamoyl imidazolium-5 (4)-olate with 1, 2, 3, 5-tetra-O-acyl-β-D-ribofuranose in the presence of Friedel-Crafts catalysts (SnCl₄, TiCl₄) followed by deacylation. It was identical with natural bredinin. The absolute configuration was established as 4-carbamoyl-1-β-D-ribofuranosyl imidazolium-5-olate.

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