Syntheses of DL-2-piperidinemethanol (XXXIII) and meso-cis-2, 6-piperidinedimethanol (XXXIV) were accomplished through a few steps from 2-picoline (I) and 2, 6-lutidine (II) respectively. The configuration of XXXIV was confirmed. The following reactions of synthetic intermediates were also examined. 6-Methylpicolinaldehyde (IX) was obtained by acetolysis followed by hydrolysis from 2-bromomethyl-6-methylpyridine 1-oxide (X) through α-bromo-6-methyl-2-pyridinemethanol acetate (XIV) in a yield, 16.2% and from 2-ethylthiomethyl-6-methylpyridine 1-oxide (XII) through α-ethylthio-6-methyl-2-pyridinemethanol acetate (XVII) in a yield, 84.2%. Unusually enough, alkaline treatment at room temperature converted 2-bromomethylpyridine 1-oxide (XIX) to 2, 2'-oxydimethyldipyridine 1, 1'-dioxide (XXVI) in a yield as high as 88.3%. The ether formation was found in the same treatment of analogues.

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DL-2-Piperidinemethanol (I) was converted to O-acyl, 2-isothioureido and oxazolidine derivatives to be subjected to reactions such as acyl migration, transguanylation and oxidation with bromine respectively. The xanthate (XIII) derived from the N-methyl derivative of I (XII) was thermally rearranged to the corresponding dithiolcarbonate (XIV). In particular, I was converted to DL-1-azabicyclo[4, 1, 0]heptane (XXIV) via DL-2-piperidinemethanol hydrogen sulfate (XXIII). XXIV was easily polymerizable and therefore, stabilized in the form of picrate for identification. Structural proof for XXIV was provided from results of reactions to which it was subjected. In conclusion, the reaction sequences of I and XII were similar to those of acyclic analogues as be theoretically expected.

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Nous avons etudie que la reaction a froid entre du dicetene et de l'hydroxylamine ou de l'acide arylsulfonhydroxamique ne donne que la methyl-3 isoxazolin-2 one-5 (I) ou son derive N-arylsulfonyle. D'autre part, un acide hydroxamique ordinaire peut se transformer a son esther sous l'influence de l'action dehydrolysante du dicetene. De plus, nous avons demontre que le compose (I) s'est change en ses sels quaternaires par la reaction evec des bases organiques, tandis qu'il s'altere a un compose nouveau (C₁₁H₁₄O₄N₂) en presence d'un acide puissant. La relation reciproque des composes dans cette serie a ete poursuivie avec succes.

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Nereistoxin (I) was synthesized from 1, 3-bis(benzylthio)-2-propanol (III) via the intermediates (VI), (XIII), and (XV). The structures of some synthetic isomers were also discussed.

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Metabolic products of sulfadimethoxine excreted in human urine were examined and three metabolites were separated. Unchanged sulfadimethoxine and N⁴-acetylsulfadimethoxine were confirmed by paper chromatography and electrophoresis. And, the other one was sulfadimethoxine-N-glucuronide, and the methyl acetyl derivative of the glucuronide was confirmed sulfadimethoxine-N¹-methyl-(tri-O-acetyl-β-D-glucopyranosid)uronate-N⁴-acetate. Sulfadimethoxine-N-glucuronide found in human urine was decided to be sulfadimethoxine-N¹-β-D-glucopyranoside or its lactone form.

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The stems of Marsdenia tomentosa contain a glycoside mixture. The alkaline hydrolysate of the crude aglycones showed the presence of sarcostin and two new aglycones. The structures of those two new materials, tomentogenin and dehydrotomentogenin has been proved. Tomentogenin was shown to be identical with 5α-dihydroutendin and dehydrotomentogenin with utendin. The structures of these latter materials were determined about the same time as this work by Reichstein.

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The roots of Metaplexis japonica MAKINO has proved to contain a glycoside mixture. The acidic hydrolysates of the crude glycoside showed the presence of metaplexigenin and two new aglycones. The structure of metaplexigenin was determined.

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Meta-, and p-substituted nitro-, amino-, dimethylamino-, diethylamino-, hydroxy-, methoxy-, chloro- and fluoro-phenobarbital were synthesized. The shortening effect of these compounds, prominal, hexobarbital and α-3-hydroxyhexobarbital on the duration of hexobarbital hypnosis in rats was compared with that of phenobarbital. Meta-, and p-chloro- and fluoro-phenobarbital, prominal and phenobarbital showed the most potent shortening effect among above all compounds. Para-hydroxyphenobarbital and α-3-hydroxyhexobarbital, the hydroxylated metabolite of phenobarbital and hexobarbital, respectively, were less effective stimulator. Para-substituted nitro-, amino-, dimethylamino- and diethylamino-phenobarbital exhibited no stimulation, while corresponding m-derivatives and m- and p-methoxy-phenobarbital showed certain activities. Pretreatment of rats with m-chlorophenobarbital also markedly activated the metabolism of hexobarbital in vitro.

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The nuclear magnetic resonance spectra of fourteen anhydro and dihydrofuranose derivatives were measured and it was found that in these compounds the coupling between anomeric C₁ hydrogen and C₂ hydrogen was very small. This does not coincide with the Karplus equation. The conformational structures of these compounds were discussed.

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The structures of the reaction products, III, IV, and V, obtained in the interaction between quinazoline and acetone, 2-butanone and cyclohexanone in the presence of hydroxide anion at room temperature, were determined to be 1-(3, 4-dihydro-4-quinazolinyl)-4-hydroxy-4-methyl-2-pentanone (III), 1-(3, 4-dihydro-4-quinazolinyl)-4-hydroxy-3, 4-dimethyl-2-hexanone (IV) and 2-(3, 4-dihydro-4-quinazolinyl)-6-(1-hydroxycyclohexyl)-cyclohexanone (V). The possible mechanism for this reaction was suggested in Chart 4 in the text.

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In order to test the analgesic action of 2, 3, 4, 5-tetrahydro-6H-1, 5-methanobenzo-[f][1, 4]diazocine (III), methods for its synthesis were examined using various starting materials. Compounds (XIII, XVI, and XVII) were synthesized from isoquinoline (IV) via 4-aminoisoquinoline (VI). Cyclization of compounds (XIII, XVI, and XVII) gave the objective azabenzomorphane derivatives (XIV, III, and XVIII), respectively. Reduction of lactam (XVIII) with lithium aluminum hydride and debenzylation of XIV by catalytic hydrogenation in the presence of Adam's platinum afforded the same objective compound (III), which was also recognized as benzoyl and acetyl derivatives (XIV and XX).

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In order to test the analgesic action of 1, 2, 3, 4, 5, 6-hexahydro-2, 6-methanobenzo[e][1, 4]diazocine (III), tetrahydroquinoline derivative (VIII) was synthesized from 2, 4-quinolinedicarboxylic acid (V) as a starting material. Reduction of VIII with lithium aluminum hydride in dioxane gave a mixture of an objective 2-aminomethyl-1, 2, 3, 4-tetrahydro-4-quinolinemethanol (IX) and 1, 2, 3, 4-tetrahydro-4-quinolinemethanol (X), the latter of which was identical with an authentic sample prepared from the acid (V). Chlorination of IX with phosphoryl chloride, followed by cyclization with potassium carbonate in xylene, gave the objective compound (III), which was derived to XIV by benzoylation.

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Both electrophysiological test and sensory test revealed that the gustatory effect of substance which show taste sour, as acetic acid and citric acid, or taste salty, such as sodium chloride and potassium chloride, was remarkably reinforced by inhibition of cholinesterase on the tongue. Where as almost no changes were observed for bitter taste or sweet taste or sugar. From these results it could be concluded that cholinesterase which is found at the gustatory nerve ending may play some important roles in the gustatory mechanism of sour and salty taste.

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14, 15-Epoxy and 15-oxo derivatives of 3β-acetoxy-5β, 17α-cardenolides were described. Epoxidation of 14-double bond of the 17α-cardenolide with monoperphthalic acid resulted in the formation of 14β, 15β-epoxide, contrary to the 17β-isomer.

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On hydrogenation of dianhydrogitoxigenin with palladium catalysts, 3β-hydroxy-5β, 14β, 17α-card-20(22)-enolide and the 20-isomers of 3β-hydroxy-5β, 14β, 17α-cardanolides were obtained. The stereo chemistry of the products are also described.

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The feasibility of gas chromatographic techniques for the separation of triterpenes has been investigated. The relative retention times of ursane, oleanane and lupane groups were examined using SE-30 phase and some correlations betweens structures and retention times were discussed.

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Gas chromatographic behaviors of seventeen kinds of hopane-zeorinane group and of twelve kinds of onocerane group were investigated using NGS and SE-30 phases. The relationships between the position of double bond and the effect to the retention time were discussed.

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The crystalline dilactone (IV) of D-glucosaccharic acid (I) derived from both 1, 4-lactone (II) and 3, 6-lactone (III) was found to be identical, and its structure was established as 1, 4-3, 6-dilactone. It was confirmed that the rapid mutarotation of IV in aqueous solution was attributable to the instability of its 1, 4-γ-lactone ring.

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The acid dissociation constants of D-glucosamine (I) and its three O-methyl derivatives were determined by titration method. The stability of I was also studied representing these compounds by the improved Fehling method preceding to the pH titration, and I was found to be stable in aqueous solution under experimental conditions. From the analysis of the titration data, I could be verified to behave as a mono basic acid by the comparison of the experimental titration curve with the one theoretically calculated. Finally, the pKa values of these four compounds were calculated.

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Stability constants and equilibrium constants of seven metal complexes of D-glucosamine (I) with Cu, Pb, Zn, Co, Cd, Ni, and Mn were determined by pH titration methdo. The possibility of complex formation of I with metal ions were examined and Bjerrum's method for calculations of stability constants was also studied, and was found to be applicable to these metal complexes. Complexes having a 1 : 1 and 2 : 1 of I to a metal ion were formed in the solution and their stability constants were calculated. Copper complexes were found to be the most stable compound and had the largest log K₁ and log K₂ values among these metal complexes. From the results of hydrolysis constants calculated of these complexes, the copper complex was found to be most susceptible to hydrolysis. Further study showed that the dimerization of complex occurred only in the case of the copper complex. Consequently, the formation path way and the possible structures for these metal complexes were proposed based upon the experimental data.

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Spectrophotometric behaviors of copper-, nickel-, and cobalt-complexes of D-glucosamine (I) were investigated in visible region. It was found that three metal ions formed a complex having a 1 : 1 ratio of I to a metal ion respectively. Equilibrium and stability constants were also determined by the application of McConnel-Davidson's method. Both stability constants of copper- and cobalt-complexes were of the same magntitude, but that of nickel-complex was lower than the other. A possibility of the presence of the hydroxo complex in the complex formation between I and metal ions was also ascertained by the analysis of the spectra at near ultraviolet region. Futhermore, the preparation of copper complex in solid state was carried out, and a 1 : 1 complex was obtained. From the analysis of the prepared complex, GCu(OH)Cl seemed to be the most probable experimental formula for the complex.

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The isotopic acyl exchange between p-nitrophenyl acetate and acetic acid was studied in neutral organic solvents in the presence of several kinds of bases. The kinetics showed the first order dependency of the exchange rate on the base. The exchange reaction is shown to consist of the two steps. The preliminary step produced the pyridine-acetic acid complex which participated in the true exchange step. The effect on the exchange rate of structural changes of the base was attributed to changes in base strength and steric effect, and they affected the preliminary equilibrium. Solvent effect on the exchange rate and curvature of k vs. [Base] were due mainly to effect on the true exchange step and partly to effect on the preliminary step.

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The isotopic acyl exchange reaction between various phenyl acetates and acetic acid was studied in pyridine solution. No steric effect on the exchange rate was observed in the case of o-substituted phenyl acetate, but the polarity of the substituents existing on the benzene ring afforded remarkable effects on the exchange rate. The electron-attracting group on the benzene ring promoted the exchange reaction. Kinetic data showed that the reaction center of the ester was the carbonyl carbon atom. The nucleophilic reactant which was formed by the preliminary reaction attacked the reaction center in the ester, followed by the bond migration which was the true exchange step and was considered to be rate-determining step. The substituents on the benzene ring gave the polar effect on the rate-determining step.

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The exchange reaction of various phenyl benzoates took place in pyridine, and the kinetic order showed identity with the result of phenyl acetates. The exchange reactions of phenyl benzoates were generally slower than that of the corresponding acetates. Relative rates of the exchange reactions were compared with that of the base-catalysed hydrolysis, and the effect on the exchange rate caused by the structural change of acyl component was attributed to the steric and electronic effects on the reaction of the ester. These effects were smaller than polar effect caused by the substituents on the phenol ring. The rate-determining step was controlled by lability of the ester bond, which was related to pKa values of the corresponding phenols.

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The sterols from Xanthii Fructus and Phellodendri Cortex were reinvestigated using gas chromatography. Gas chromatographically pure stigmasterol. β-sitosterol and campesterol were obtained by a repeated recrystallization of either acetate or benzoate of the sterol mixture. γ-Sitosterol isolated from Phellodendri Cortex and also from soybean was found to be a mixture of campesterol and β-sitosterol (1 : 1).

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Emodin, ω-hydroxyemodin, and emodic acid were isolated from Talaromyces avellaneus C.R.BENJAMIN (conidial stage : Penicillium avellaneum THOM et TURRESON). Skyrin was proved to be the main pigment of Preussia multispora CAIN.

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Copper complexes of methyl-β-D-glucosaminde (II) and 3, 4, 6-tri-O-methyl-D-glucosamine (III) were investigated by pH titration method. The sability constants log K₁ and hydrolysis constants pK_LCu(OH) of these two complexes were determined and compared with that of copper complex of D-glucosamine (I). The magnitude of log K₁ of copper complex of II was the same to that of copper complex of III, but both of them were slightly smaller than that of copper complex of I. However, the hydrolysis constants of copper complexes of I, II, and III were of the same order in the magnitude.

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