Reaction of bicyclic conjugated dienones (II, III, IV, V, and VI) with hydrazoic acid in PPA was carried out and the results were summarized in Table I. All products were probably formed by action of two molar equivalents of hydrazoic acid. From the substrates (I and III), the aldehyde-lactams (XI, XIX, and XX) were obtained whose formation is the first observation in this reaction.

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Mechanism of the absorption of drugs from oil in water emulsions to which emulsifier was added at higher concentration was studied in rat large intestine, using in situ recirculation technique. Synthesized esters of fatty acids, tri-n-butyrin and ethyl laurate as oil and polysorbate-80 as emulsifier were chosen. Two model drugs, vitamin A acetate (VAA) and phenylbutazone (PB) were chosen for absorption studies. VAA was distributed into oily, and micellar phases, not into aqueous phase. Oil/micelle partition coefficient of VAA was determined using ultrafiltration method. PB was distributed into oily and micellar phases, and a few into aqueous phase in spite of its nearly complete ionization at neutral pH. In the absorption of VAA, amount of the drug in micellar phase was a critical factor for absorption as VAA was absorbed mainly via micellar phase. VAA was released from micelles adsorbed on mucosal layer and was absorbed, and this process was interfered with oil droplets adsorbed on mucosal layer. In the absorption of PB, amount of the drug in aqueous phase was a critical factor for the absorption as PB was absorbed mainly via aqueous phase. Absorption process of PB was not interfered with oil droplets adsorbed on mucosal layer.

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Absorption of drug which is adsorbed at oil-water interface in emulsion was studied in rat large intestine using in situ recirculation technique. Methyl orange (MO) which was chosen as a model drug, was adsorbed at oil-water interface by the coexistence with emulsifiers. Its physico-chemical states were varied with oil concentrations. MO was absorbed well more than ten times from emulsion system compared with that from aqueous solution. Enhancement of MO absorption was interrelated with the adsorption of MO at oil-water interface. Furthermore it was found that not only quantity but also quality of MO adsorption at oil-water interface affected on the absorption rate of MO. Critical oil concentration which showed maximum absorption rate, depended on the length of the absorption site and the degree of adsorption of oil droplets on mucosal membrane was also rate-determining factor for MO absorption from emulsion system.

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The distribution and changes of concentration of cyclocytidine in tissues with time were quantitatively examined after intravenous injection or oral administration. Localized distribution of the compound in tissues was confirmed quantitatively and retention of the compound in most of the tissues tested was found out. Whereas, aracytidine distributed uniformly in tissues and elimination rate of the compound from tissues was similar in each other. After oral administration, cyclocytidine distributed in various tissues at very low levels.

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Binding properties of the rat liver cytoplasmic organic anion binding proteins, Y and Z proteins, for two organic anionic model compounds, bromphenol blue (BPB) and amaranth (AM) which are transported from blood stream into the rat bile by an active transport system, were studied by means of chemical methods, modifying the proteins with sulfhydryl-blocking reagents and amino group modifiers and fluorescent probe. Moreover, the affinities to Y and Z proteins were compared with that to bovine serum albumin by means of the apparent association constants. AM had higher affinity to the liver proteins than to bovine serum albumin, but in the case of BPB reverser result was obtained. The hydrophobic binding is important for the bindings of the dyes to the both proteins and BPB had higher affinities to the both proteins than AM. However, the binding properties to the both proteins were different, namely the binding of AM to Y protein was thought to be mainly due to the hydrophobic forces but the contribution of ionic forces could not be neglected with respect to the binding of BPB to the both protems.

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After the administration of antipyretics, the pharmacological response intensity versus time course was expressed quantitatively using a pharmacokinetic method. Acetaminophen and 4-aminoantipyrine were used as the antipyretics. After the administration of these drugs, plasma level, brain level and urinary excretion of the drug were determined as the drug disposition data. Metabolic rate, vaporization rate, rectal temperature and skin temperature were also determined as the pharmacological effects. From the observed data, an electrical analog was constructed to simulate the effects of antipyretics including physiological thermoregulation. The results indicate that the time course of pharmacological effects are reasonably simulated by a single mathematical model.

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The direct reaction of quinazoline 3-oxide (I) with ketones (III) without a base was carried and resulted in the transformation of I into quinoline derivatives (II), although the yields of II were very poor (small percentage) in some cases. Thus, the reaction of I with acetophenone gave 2-phenylquinoline (II-3), quinazoline (IV) and 4, 4'-biquinazoline (V), with propiophenone, 3-methyl-2-phenylquinoline (II-4) and V, with acetone, 2-methylquinoline (II-5), IV, V, and 2-aminobenzaldoxime (VI), with 3-pentanone, 2-ethyl-3-methylquinoline (II-6), IV and VI, with 2-butanone, 2, 3-dimethylquinoline (II-7) and IV, with 2-pentanone, 3-ethyl-2-methylquinoline (II-8), IV and VI, with 3-methyl-2-butanone, 2-isopropylquinoline (II-9), IV and 4-methylquinazoline 3-oxide (VII), with 3, 3-dimethyl-2-butanone, 2-tert-butylquinoline (II-10), IV, V, and VII, with 4-methyl-2-pentanone, 2-isobutylquinoline (II-11), IV and V, with cyclopentanone, 2, 3-dihydro-1H-cyclopenta [b] quinoline (II-12), with cyclohexanone, 1, 2, 3, 4-tetrahydroacridine (II-13), respectively.

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Some new N¹-substituted 3, 5-dimethyl (I), 4-arylazo (II) pyrazoles, N¹-substituted 4-arylhydrazono-2-pyrazoline-5-ones (III) and N¹-substituted 2-pyrazoline-5-ones (IV) have been synthesised by the condensation of aroyl/aryloxyacetylhydrazine with 2, 4-pentanedione or arylhydrazones of 2, 3, 4-pentanetrione and ethyl 3-oxobutyrate respectively. Some oxalyl/adipyl-1, 1'-bis-3, 5-dimethylpyrazoles (V) and oxalyl/adipyl-1, 1'-bis-3-methyl-2-pyrazolin-5-ones (VI) have also been prepared by the reaction of oxalyl/adipylhydrazine with 2, 4-pentanedione and ethyl 3-oxobutyrate respectively.

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The relative ratio of three forms of N, N'-dimethylpiperazine in aprotic solvent was determined at room temperature by analyzing the curve of dielectrometric titration. The molar ratios of forms I, II, and III at 30° in dioxane were 0.880, 0.116, and 0.004, respectively, which were in good agreement with those of Allinger, et al. had obtained from the dipole moment of free diamine in benzene solution. The use of dielectrometric titration seemed to afford a particularly simple and direct method for conformational analysis of aliphatic di-tertiary amines.

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A large scale preparation of 2-haloadenosines (1) was attained by acetylation of 2-haloinosines (3), followed by chlorination and amination. 2-Alkoxyadenosines (5) were prepared in fairly good yields by protection of both 2'- and 3'-hydroxyl groups of 2-chloroadenosine (1a) or 2-chloroinosine (3a), followed by substitution of the chlorine atom with alkoxy group. In the reaction of 1a with sodium alkoxide, there were obtained some oligomers of 5, of which the structures were elucidated. The reaction of 5-amino-4-cyano-1-β-D-ribofuranosylimidazole with carbon disulfide afforded 2, 6-di-mercapto-9-β-D-ribofuranosylpurine (15), which was converted to 2-mercaptoadenosine (14e) and its S-substituted derivatives. 2-Phenylaminoadenosine (29e) was prepared with comparative ease via 2-phenylamino-2', 3', 5'-tri-O-acetylinosine (32), the synthesis of which was effected by acetylation of 2-phenylaminoinosine (30) with acetylchloride in acetic acid. Many 2-substituted adenosines including O-substituted 2-hydroxyadenosines, S-substituted 2-mercaptoadenosines, N²-substituted 2-aminoadenosines, 2-alkyl- and -aryl-adenosines were prepared, among which several compounds were found to have a remarkable coronary vasodilating potency. Compound (29e) showed not only a strong potency, but also a longer duration of the effect than that of 1a. The structure-coronary vasodilating activity relationship was also discussed.

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Absorption characteristics of highly lipid-soluble dyes from oil-in-water emulsions was studied in the rat small intestine. Short-chain triglyceride or long-chain triglyceride was chosen as an oil phase and absorption of oils as well as dyes (Oil Red XO and Sudan Black B) was investigated using in situ loop method. From emulsions using tributyrin as an oil phase, Oil Red XO was absorbed monoexponentially to the same extent as from Polysorbate-80 micellar solution despite the fact that the dye is very lipophilic and is not considerable to be localized in the aqueous phase. On the other hand, from emulsions using triolein as an oil phase, Oil Red XO was absorbed faster in the early stage and slower in the later stage than from tributyrin emulsions. These absorption characteristics of Oil Red XO was demonstrated as the reflection of that of oils. Oil Red XO does not seem to move into inner compartments with oil, for it was not transported into intestinal lymph even from triolein emulsions.

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Lymphatic transport of lipid-soluble dye, Sudan Blue, and vitamin A acetate from oil-in-water emulsions was investigated using in situ loop method by the rat small intestine. A natural oil, triolein, which was known to be transported mainly through lymphatic pathway, was chosen as an oil phase of the emulsion. Lymphatic transport of Sudan Blue and vitamin A acetate was very small in the absence of bile. When sodium taurocholate and egg phosphatidylcholine were co-administered with emulsions, lymphatic transport of lipid-soluble compounds were recovered even in bile fistula rats. Addition of one of them could not recover completely the lymphatic transport of lipid-soluble compounds. It was concluded that both bile salts and phosphatidylcholine were necessary for the lymphatic transport of the fat and lipid-soluble compound which interact with oil administered intraluminally. However, overall contribution of lymphatic pathway to their disappearance from the small intestinal lumen is very small, and the main route of their absorption is thought to be the portal pathway.

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The studies on the mechanisms involved in the selective O-methylation of the catechol estrogen in the rat have been undertaken. Both in vitro and in vivo experiments revealed that the catechol 2-glucuronide and 3-sulfate underwent O-methylation preferentially at the unconjugated phenolic group yielding the 3- and 2-monomethyl ethers, respectively. It was also demonstrated that the catechol monoglucuronide was directly transformed into the corresponding methyl ether with retention of the glycoside linkage. These results are indicative of the active participation of conjugation in the metabolic transformation of steroid hormones in the living animals.

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The degradation rate of active ingredient of drugs in homogeneous or heterogeneous system was found to conform to a rate equation within a range of degradation ratio. The equation was obtained by using a Weibull probability paper [numerical formula] where α is degradation ratio, t is time, and m and k are parameters. The rate equation was corresponded to usual reaction rate equations. As a result, it exhibits good approximation within the range of degradation ratio of 1-30%, and the Arrhenius equation can be applied to these parameters. In the present investigation, acetylsalicylic acid solution, ascorbic acid solution, ascorbic acid-mannitol powder, and pyridoxal phosphate solution were used to exemplify those points. As a result, the degradation ratio predicted was in good agreement with those observed. It may be concluded that a method by the Weibull probability paper suggested in the present paper is useful on account of its convenience and accuracy of the prediction compared with usual ones by reaction kinetics.

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For prediction of stability of drugs upon storage attended by temperature change, the multilevel nonisothermal method that estimates stability from degradation ratio after a specific period in straight temperature increase process was proposed. The theoretical consideration for this method and the development of an apparatus were made and the graphical method was employed for calculation. Several drugs were used to test this method. As a result, the values predicted by the graphic calculation were consistent with the values observed after storage in a warehouse. It is considered that the present method is a useful means for quality assurance of drugs.

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The action on various smooth muscle of 1-diethylaminoethyl-3-(p-methoxybenzyl)-2-quinoxalone (P 201-1) and its inhibitory effect on the phosphodiesterase (PDE) activity in the supernate prepared from the rat ileum, cerebral cortex, and liver were investigated by comparison with those of papaverine. P 201-1 had more potent antispasmodic action on the isolated guinea pig ileum, gastric smooth muscle and uterus of the rat, rabbit ileum and so on than papaverine, and showed little influence upon the autonomic nervous system. P 201-1 inhibited the PDE activity in the supernate prepared from the rat ileum, cerebral cortex, and liver. The Ki values of P 201-1 for the supernate of the ileum, cerebral cortex, and liver were 1370, 700, and 650 μM, respectively, and the values were 5-10 times those of papaverine. The inhilitory effect of P 201-1 on PDE from the rat ileum or cerebral cortex was competitive and that from the liver noncompetitive, and the type of inhibition of P 201-1 was different from that of papaverine in each tissue. When the influence of Mg²⁺ concentration on the inhibitory effect of P 201-1 was examined, the liver PDE inhibition of P 201-1 occurred in a different way from the ileum or cerebral cortex PDE inhibition, and completely disappeared at high concentration of Mg²⁺ (10 mM).

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To elucidate the relationship between chemical structure and their biological activities, the contents of cytochromes and hepatic constituents in addition to the activities of drug-metabolizing enzymes and δ-aminolevulinic acid (δ-ALA) synthetase were examined in rats treated with various chlorinated benzenes, i.e., monochlorobenzene (MCB), p-dichlorobenzene (p-DCB), 1, 3, 5-trichlorobenzene (1, 3, 5-TRCB), 1, 2, 4, 5-tetrachlorobenzene (1, 2, 4, 5-TECB), pentachlorobenzene (PECB) and hexachlorobenzene (HCB). 1) The content of cytochrome P-450 and activities of aminopyrine demethylase and aniline hydroxylase were increased by oral administration of all chlorobenzenes except MCB at daily dose of 250 mg/kg, once daily, for 3 days. The contents of microsomal protein and phospholipids also showed a similar tendency to those as described above. The activity of δ-ALA synthetase was increased by treatment with all compounds used. 2) The content of cytochrome P-450 and activity of aminopyrine demethylase were decreased in 24 hr after a single administration of MCB in doses of 125, 250, 500 and 1000 mg/kg, whereas the activity of δ-ALA synthetase was increased markedly by all doses used. The activity of aniline hydroxylase was increased by a dosing of 1000 mg/kg MCB. 3) In the time-course after a single administration of MCB in a dose of 250 mg/kg, the activity of δ-ALA synthetase was decreased in 6 hr after administration, and subsequently restored to normal levels in 12 hr, and then increased markedly in 24 hr. The opposite changes were noted in the content of cytochrome P-450.

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Hepatic constituents and the cytochrome contents in addition to activities of drugmetabolizing enzymes and δ-aminolevulinic acid (δ-ALA) synthetase were examined in rats treated with each isomer of dichlorobenzene (DCB), trichlorobenzene (TRCB) and tetrachlorobenzene (TECB) in an oral dose of 250 mg/kg once daily for 3 days. 1) In the studies on DCB-isomers, activities of aminopyrine demethylase and aniline hydroxylase were enhanced markedly by treatment with m-DCB, whereas cytochrome content was not altered significantly by treatment with any DCB-isomers. δ-ALA synthetase activity was enhanced 63, 32 and 42% by treatment with o-, m- and p-DCB, respectively, but these enhancement were not paralleled with the changes in cytochrome P-450 content. 2) In the administration of TRCB-isomers, enzyme activities were enhanced markedly by treatment with 1, 2, 4-TRCB. Cytochrome P-450 content was also increased by treatment with 1, 2, 4-TRCB, and this increase could be partly related with the enhancement of δ-ALA synthetase activity. 3) By treatment with all TECB-isomers, activity of aminopyrine demethylase was enhanced, whereas aniline hydroxylase was not altered. Cytochrome P-450 content was increased by treatment with all TECB-isomers. 4) Microsomal protein content was increased with all isomers of DCB, TRCB and TECB treatment. Microsomal Pi was increased markedly 36, 70 and 91% by treatment with m-DCB, 1, 2, 4-TRCB and 1, 2, 3, 5-TECB, respectively. Hepatic glycogen content was decreased only by 1, 2, 3, 5-TECB, but triglyceride content was not altered. 5) The spectral change induced by substrate-cytochrome P-450 binding was characterized by type I in each treatment, but conversion of the type occurred in treatment with 1, 2, 4, 5-TECB in high concentration of 1 mM.

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The contents of hepatic constituents and cytochromes as well as the activities of drug-metabolizing enzymes and δ-aminolevulinic acid (δ-ALA) synthetase were determined in rats treated with 1, 2, 4-trichlorobenzene (1, 2, 4-TRCB). 1) Liver weight and microsomal protein content were increased in higher doses than 750 mg/kg 24 hr after the administration, but in contrast glycogen content was markedly decreased in higher doses than 500 mg/kg. In a dose of 250 mg/kg and above, the activities of aminopyrine demethylase and aniline hydroxylase, cytochrome P-450 contenn were increased, but on the contrary cytochrome b₅ content showed the tendency to be decreased in high doses. δ-ALA synthetase activity was increased in higher doses than 250 mg/kg, and this increase attained approximately 300% in higher doses than 750 mg/kg. 2) In a single oral dose of 500 mg/kg, glycogen content was decreased markedly from 6 hr after the administration and this decrease was maintained for 48 hr. The increase of microsomal protein content was noted in 3 hr after dosing, but cytochrome P-450 content, activities of aminopyrine demethylase and aniline hydroxylase were increased 24 hr after the administration. These increases were maintained for 5 days, especially in aminopyrine demethylase for 15 days. δ-ALA synthetase activity was decreased markedly in the early stage, that is, 3 or 6 hr after the administration, but increased rapidly after 24 hr. 3) An apparent parallelism between the change in δ-ALA synthetase activity and that in cytochrome P-450 content was not noted.

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Artificially created cluster technique has been used for the quantitative determination of serum levels of 1-piperidino-2, 4'-dimethylpropiophenone (Mydocalm). A mixture of unlabeled drug and stable isotope labeled drug (Mydocalm-¹⁵N) was orally administered for identification of Mydocalm. Decadeuterium labeled Mydocalm (Mydocalm-d₁₀) was prepared and used as an internal standard and carrier for determination. A 100 mg dose of Mydocalm has been given orally to 3 subjects.

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Treatment of pyrimidine nucleosides with hydroxylamine-O-esters (or hydroxylamine-O-aryl ethers) produced the corresponding 3-amino derivatives. 3-Aminouridine derivatives underwent deamination and acetylation to give uridines and 3-acetamidouridines, respectively. 3-Aminocytidine derivatives underwent, in addition to deamination, replacement with a sulfhydryl and cyclization with an orthoformate to give 3-amino-4-thiouridine and 1, 2, 4-triazolo [2, 3-c] pyrimid-5 (6H)-one derivatives, respectively. Proton magnetic resonance and ultraviolet data of 3-amino derivatives are tabulated.

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l-Sparteine was titrated with p-tert-butylbenzenesulfonic acid in dioxane at room temperature and the N-formed titration curve was obtained. The moment angle between two ion-pairs of l-sparteine-disulfonate calculated from the titration curve was found to be 138°10', which differed much from the value of 93°02' calculated from the conformation of free l-sparteine determined by Bohlmann, et al. But our optical rotatory dispersion study of the solution in the titration process proved that nearly 100% inversion occurred in A-ring when l-sparteine-monosulfonate became its disulfonate by the titration. The moment angle of new conformation was calculated as 139°44'which was in good agreement with the observed value of 138°10'.

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After several preliminary experiments, enmein (1) was converted into enmelol (2). The route consists of the following steps : (i) Enmein (1) was converted into lactone ester 40 via 3, 8, 9, and 10. (ii) An acyloin product 42 derived from 40 was transformed into 15-kaurene derivative 61, via epoxide 56, 1β-ol 57, acetate 58, and 15-ol 59. (iii) By photosensitized oxygenation of 61, allyl alcohol 62 and αβ-unsaturated ketone 63 were yielded. (iv) Enmelol (2) and 15-epienmelol (69) were derived from 63 and 62, respectively.

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Of twelve compounds so far isolated from the underground parts of Trillium kamtschaticum PALL., eight steroid saponins, Ta, Td, Tb, Tc, Tg, Te, Tk and Tf, were characterized, respectively, as follows : prosapogenin A (VII) of dioscin, mp 242-246° (decomp.), [α]_D- 108.3° ; a furostanol bisglycoside (VIII) corresponding to VII, mp 265-271°(decomp.), [α]_D -83.1°; pennogenin 3-O-α-L-rha. pyr-(1→2)-β-D-glc·pyranoside (X), mp 273-276°(decomp.), [α]_D -117.8° ; pennogenin 3-O-β-chacotrioside (XI), mp 297-299°(decomp.), [α]_D -126.7° ; pennogenin 3-O-α-L-rha·pyr-(1→4)-[α-L-rha·pyr-(1→2)]-β-D-glc·pyranoside (XII), mp 224-228° (decomp.), [α]_D -136° ; the proto-type compound (XIX) of X, mp 275-280°(decomp.), [α]_D -84.6° ; kryptogenin 3-O-β-D-glc·pyranoside (XXIII), mp 238-241° (decomp.), [α]_D -129.4° ; 26-O-β-D-glc·pyr-17 (20)-dehydrokryptogenin 3-O-α-L-rha·pyr-(1→2)-β-D-glc·pyranoside (XXIV), mp 265-268° (decomp.), [α]_D -80.1°. X, XI and XII are the first pennogenin glycosides ever reported and XXIII has never been isolated either. Marker's "nolonin" (VI) was presumed to be a furostanol 3, 26-O-bisglycoside such as XIX corresponding to X, and the structures of nologenin (V) and VI were supposed to be represented as V' and VI', respectively. XXIV was regarded as an artefact yielded from XIX during chromatography over silica gel.

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β-Glucuronidase activity in rat serum was found to be considerably elevated by a single injection of organophosphorus insecticides. In order to elucidate this mechanism, the intracellular distribution of β-glucuronidase in the liver was investigated. The extent of increase of β-glucuronidase in serum of diazinon treated rat was shown to correlate with the degree of decrease in microsomal fraction of liver. After the administration of diazinon, β-glucuronidase in the microsomal fraction was held constant at low level for 10 days and a period over 30 days was required to recover the normal level.

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Aliphatic aldehydes can be detected and determined by reaction with propionaldehyde (3-phenyl-2-quinoxalinyl) hydrazone in ethanolic solution. The red color is produced within 20 min at 40°, then faded gradually. Detectable responses are obtained with aliphatic aldehydes but not with aromatic aldehydes, glucose, and ketones. With acetaldehyde, propionaldehyde, butyraldehyde, and iso-butyraldehyde, absorbance of the reaction mixture measured at 465 nm is directly proportional to the concentration. Acetaldehyde can be determined in the concentration range of 5×10^-5 to 1×10^-3M and other aldehydes in the range of 1×10^-4 to 1×10^-3M.

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N, N-Dibromobenzenesulfonamide (II) was allowed to react with trans-isosafrole (I) in various molar ratios in dichloromethane, and an unexpected product, N-benzenesulfonyl-2-bromo-4, 5-methylenedioxyaniline (V) was isolated other than the adducts, erythro-1-benzenesulfonamido-2-bromo-1-(3', 4'-methylenedioxyphenyl) propane (III) and its 6'-bromo-substituted analogue (IV). And their structures and synthesis were investigated.

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The purpose of this study was to clarify the competition and the mechanism of intestinal absorption of various cationic drugs by in situ and in vitro techniques. As model drugs, pralidoxime iodide (2-PAM) and several amine drugs were employed. Although the absorption of 2-PAM and 2-allyloxy-4-chloro-N-(2-diethylaminoethyl) benzamide hydrochloride (A. C. D. B.) became saturated when drug concentration increased, they might not be absorbed actively. Nine amine drugs including A. C. D. B. competitively inhibited the absorption of 2-PAM. Furthermore, the absorption of A. C. D. B. was similarly inhibited by one of the amine drugs. No physicochemical interaction as well as direct action on the membrane permeability were observed. Since A. C. D. B. did not affect the absorption of quinine and L-tryptophan, its effect is thought to be brought on the specified drugs. Inhibitory action of the amine drugs on the accumulation of 2-PAM to the gut wall and the uptake to the epithelial cells were operative. Since pharmacologic action of amine drugs is so varied and the drugs with opposite pharmacologic action inhibit 2-PAM absorption as well, it is supposed that the molecular structures which amine drugs have in common (phenylalkylamine) may relate to the inhibitory effect. Other cationic drugs having no such group did not affect the absorption of 2-PAM at all.

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An attempt was made to elucidate the mechanisms of the drug absorption from intestine in the fasted rats. During fasting, weight of the body decreased gradually, whereas arterial hematocrit increased in proportion to the duration of food deprivation. It was observed that not only volume of blood plasma but also interstitial fluid volume decreased. These results could be interpreted as suggesting a decrease of distribution volume. In spite of the less absorption of drug from intestine, blood concentration of the fasted rats was higher than that of the controls. Volume of distribution was lost approximately 40% of the initial values during fasting for 60 hours. From these results, it was concluded that the diminished volume of distribution induced by fasting is one of the main causes which may bring about the decrease of drug absorption from intestine in the fasted rats. Other possible mechanisms were also discussed.

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Methylenebis (4-amino-5-arylpyrimidines) (IVa, IVb, VI, VIII) were obtained from 4-acetamido-5-arylpyrimidines (IIa, IIb) and 4-amino-5-arylpyrimidines (Ia, Ib, V, VII) on heating with dimethyl sulfoxide.

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Stability of the deuterium-label in the p-hydroxylation of l-ephedrine [arom.-²H₅] was investigated as one of problems on the applicability of this labeled compound to metabolic studies in man. p-Hydroxyephedrine liberated by enzymic hydrolysis from its glucuronide in the 24-hr urine of rats injected deuterated l-ephedrine (97.9 atom% ²H) was purified and oxidized to p-hydroxybenzoic acid. The deuterium content on the aromatic ring of the latter compound was found to be 98.1 atom% ²H by determining accurately by mass spectrometry. This fact indicates that the deuterium-label at meta and ortho positions of the substrate was retained during the p-hydroxylation and that the deuterium-label of the resulting p-hydroxyephedrine was stable during the glucuronide formation and the subsequent enzymic hydrolysis of the glucuronide to its free form.

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3, 6-Dimethyl-5-hydroxypyridazine 1-oxide (IV) reacted with formalin and a secondary amine such as pyrrolidine, piperidine, morpholine or 2, 2'-dihydroxydiethylamine to give the corresponding 3, 6-dimethyl-4-alkylaminomethyl-5-hydroxypyridazine 1-oxides (VIa-d). Bromination of this compound with bromine gave 3, 6-dimethyl-4-bromo-5-hydroxypyridazine 1-oxide.

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The steroid glycosides in the fresh whole plants of Heloniopsis orientalis (THUNB.) C. TANAKA were examined and the following four steroid saponins were isolated and identified : pennogenin 3-O-rhamnosyl-chacotrioside (II) ; methyl proto-dioscin ; 26-O-β-D-glucopyranosyl-25D-furost-5-ene-3β, 17α, 22, 26-tetraol 3-O-rhamnosyl-chacotrioside (III) (the proto-type compound of II) ; 26-O-β-D-glucopyranosyl-17 (20)-dehydrokryptogenin 3-O-rhamnosyl-chacotrioside (VI) (an artefact produced from III). III is the second furostanol 3, 26-O-bisglycoside corresponding to a coexisting pennogenin 3-O-glycoside and could be regarded as a "nolonin".

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The polymer support having a phenacylalkyl side chain for the solid-phase peptide synthesis was found to give a better hydrazinolysis yield than the ordinary polymer support.

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The metabolism and excretion of aminopyrine in man were examined after oral administration. On the gas chromatogram, the extract from urine showed an unknown peak sometimes which seems to be a new metabolite. This new metabolite was identified as 4-formylaminoantipyrine by gas chromatography-mass spectrometry comparing with the synthesized authentic sample.

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The structure of arnottinin (1) was established by the transformation of osthenol (2) to it.

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Im Zusammenhang mit der chemotaxonomischen Studien der Gattung Pteris und der verwandten Gattungen konnten aus Pteris kiuschiuensis HIERON. neben dem bereits bekannten Pterosin Q (I) drei neue Indan-1-on-Verbindungen, nahmlich Pterosin S (II), T (III) und U (IV) isoliert werden, deren Strukturen durch spektroskopische und CD-Daten aufgeklart werden. In allen Fallen handelt es sich um Diastereoisomerengemische.

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