The aqueous solutions of 24 benzoyl derivatives were perfused through the samll intestine of anesthetized rats. The absorption rate coefficient calculated from the slope of the straight line which was obtained from the logarithmic plots of the residual ratio vs. time was used for comparison of the intestinal absorption rates of these foreign organic compounds. In each series (benzoic acid-, benzaldehyde-, methyl benzoate-series), the absorption rate decreased as the number of hydroxyl groups increased. When comparing the monohydroxyl derivatives in each series, the o-isomer was absorbed faster than m- and p-isomers, but this was not true of methoxyl derivatives. From these facts, it is suggested that Danielli's model may be applied to the intestinal absorption of foreign organic compounds.

View full abstract

The present paper has established the kinetics and mechanisms for the general aicd-base catalysed hydrolysis of chlorothiazide (I) over the pH range 0.08-9.96 at 87.5°, which decomposes to 4-amino-6-chloro-m-benzenedisulfonamide (IV) via parallel consecutive firstorder reaction in aqueous solution : one leading to the formation of N-(2-amino-4-chloro-5-sulfamoylphenylsulfonyl) formamide (II) in aqueous alkali, and the other leading to the formation of 5-chloro-2, 4-disulfamoylformanilide (III) in acidic media.

View full abstract

The structure of aurofusarin, a golden yellow pigment of Fusarium culmorum (W.G. Smith) SACC., has been studied. A dimeric naphthoquinonepyrone structure (IIa) has been put forward for aurofusarin by the comparative spectrometric studies of diacetate (IIb) and dimethyl ether (IIc) with some reference compounds.

View full abstract

The structure of aurofusarin (Ia) was established by the biogenetical type synthesis. Rubrofusarin (IIa) was partially methylated to yield monomethyl ether A (IIb) which was converted into IIIa by oxidation with Fremy's salt. Partial demethylation of IIIa to IIIb followed by oxidative coupling using potassiumpersulphate as the reagent afforded 7, 7'-bis (8-hydroxy-5-methoxy-2-methyl-4H-naphtho [2, 3-b] pyrane-4, 6, 9-(6H, 9H) trione] (Ic), whose methyl ether was proved to be identical with aurofusarin dimethyl ether (Ib).

View full abstract

Decarboxylation of 1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid derivatives, I, II, III, IV and IV hydrochloride, in acetophenone and benzaldehyde as solvents, was examined. It was found that in the case of IV hydrochloride, 4-substituted isoquinoline derivatives were formed in moderate yield according to the solvent used.

View full abstract

The structure of a new steroidal sapogenin, diotigenin (Ia), isolated from Dioscorea tenuipes complex, was investigated, and it was assumed to be 25L-2β, 3α, 4β-trihydroxy-5β-spirostane.

View full abstract

In order to synthesize 1-substituted amino-3, 5, 5-trimethylpyrazolines, diacetonalcohol was employed as the starting material, from which mesityloxide was prepared by the treatment with a catalytic amount of iodine, followed by the cyclization with hydrazine. The resulting 3, 5, 5-trimethylpyrazoline was converted to 1-chloroacetyl-3, 5, 5-trimethylpyrazoline by the reaction with chloroacetylchloride, followed by the reaction with a variety of amine. In this process, the reaction of mesityloxide with hydrazone was deduced to proceed probably through the intermediate of the corresponding hydrazone. Moreover, 1-β-carboethoxyethyl-3, 5, 5-trimethylpyrazoline was obtained by the reaction of 3, 5, 5-trimethylpyrazoline with ethyl acrylate.

View full abstract

1-(2', 3'-Epoxy-β-D-lyxofuranosyl) isocytosine (IV) was obtained in the reaction of 2', 3'-di-O-tosyluridine (I) with methanolic ammonia through 2', 2'-anhydro-1-(3'-O-tosyl-β-D-arabinofuranosyl) uracil (II) and 2-O-methyl-1-(2', 3'-epoxy-β-D-lyxofuranosyl)-uracil (III). Ultraviolet absorption spectra of 2-substituted-uracils and their nucleosides were comparatively examined and their pK_a values were determined. From the nuclear magnetic resonance spectra it was found that amino group of isocytosine derivatives was existed as amino form and that H₁' of 2', 3'-epoxylyxosyl nucleosides did not couple with H₂' and its signal appeared as a sharp singlet.

View full abstract

1-(2', 3'-Epoxy-β-D-lyxofuranosyl) isocytosines (I) and (II) were easily deaminated by heating with aqueous hydrogen chloride, yielding 2, 2'-anhydro-1-(3'-chloro-3'-deoxy-β-D-arabinofuranosyl) uracil (III), and 1-(3'-chloro-3'-deoxy-β-D-arabinofuranosyl) uracil (IV). And other isocytosine derivatives (VIII), (X), (XI), and (XVI) were also deaminated by heating at 80° for several minutes in acetic acid to corresponding anhydronucleosides, i.e. VII, IX, and XV, while 2', 3'-O-isopropylideneisocytidine (XVII) and isocytidine (XVIII) were not deaminated. Furthermore, demethoxylation of 2-O-methylpyrimidine nucleosides was studied. In the reaction of 2, 5'-anhydro-1-(2, 3'-di-O-acetyl-β-D-arabinofuranosyl) uracil (XXI) with triethylamine in methanol, 2-O-methyl-1-β-D-arabinofuranosyluracil (XXII) was not obtained, but IX as a sole product. This phenomenon showed that XXII was the intermediate. However, 2-O-methyl-1-(2', 3'-epoxy-β-D-lyxofuranosyl) uracil (XXIII), 2-O-methyl-1-(2', 3'-O-isopropylidene-β-D-ribofuranosyl) uracil (XXIV) and 2-O-methyluridine (XXV) were not demethoxylated by heating at 80° in acetic acid. Therefore, deamination in isocytosine derivatives and demethoxylation in 2-O-methylpyrimidine derivatives required one hydroxy group of up form in 2'-position or 2', 3'-epoxide ring of lyxo-form.

View full abstract

It was found that hydantoin nuclei (Ia-d) were easily hydrolysed with caustic alkali to give hydantoic acid derivatives (IIIa-c) by way of 3-tosylhydantoin derivatives (IIa-d). IIIa-c were further hydrolyzed to amino acids with diluted hydrochloric acid. The hydrolysis of IId with alkali did not furnish the hydantoic acid derivative IIId but gave N-tolylsulfonyl-2-amino-2-isobutyl-4-methylvaleramide VI, probably due to the steric effect.

View full abstract

N, N-Disubstituierte Saureamide wurden mit P₂S₅ in Xylol erhitzt. Die erhaltenen Thiosaureamide wurden in absolutem Acetonitril mit Phenacylbromid umgesetzt. Die gewonnenen S-Phenacylsalze lassen sich mit aromatischen Aldehyden zu unbekannten Farbstoffe kondensieren. Beim Erhitzen der S-phenacylsalze in Methanol bildeten sich 2, 5-Diphenyl-1, 4-dithiin und Dimethylammoniumbromid.

View full abstract

Four possible racemates of 4-hydroxymethyldecahydroisoquinolines, hitherto unknown in the literature, were synthesized and their stereochemistry was specified and characterized. Hydrochloride salts of their benzoylesters were also prepared and their local anesthetic activity was tested, but none was proved to be useful.

View full abstract

The intermediate products yielded by the reaction of biguanides with diethyl oxalate were inferred to be (4, 5-dioxo-2-imidazolidinylidene) guanidines by means of their infrared absorption spectra. Moreover, in order to elucidate this reaction mechanism, the reaction between guanidine containing the similar structural moiety to biguanides and diethyl oxalate was examined. As the result, it was assumed that the reaction of biguanide with diethyl oxalate would proceed through the cyclic transition state to afford (4, 5-dioxo-2-imidazolidinylidene) guanidine.

View full abstract

The reaction of N-amidino-O-alkylisourea with some carboxylic esters was attempted. Condensation with diethyl oxalate in alcohol gave alkyl 4-amino-6-alkoxy-s-triazine-2-carboxylate through the formation of the five membered-ring intermediate. Alkyl 4-amino-6-alkoxy-s-triazine-2-carboxylate was easily converted into the coresponding amide with a variety of amines. Condensation with ethyl acetoacetate gave 6-methyl-2-alkoxyamidino-4-pyrimidinol and 4-amino-2-alkoxy-6-acetomethyl-s-triazine. Condensation with ethyl cyanoacetate afforded only 4-amino-2-alkoxy-6-cyanomethyl-s-triazine, but not any expected pyrimidinol. Condensation with ethyl chloroacetate gave 4-amino-2-alkoxy-6-chloromethyl-s-triazine, which was converted into 4-amino-2-alkoxy-6-substituted amino-s-triazine with a variety of amines.

View full abstract

Amino acid derivatives bearing an actinomycin chromophore was synthesized in a hope of finding one or another with more carcinolytic activity and less toxicity than the actinomycin. That is, DL-valine ethylester, DL-serine ethylester, DL-phenylalanine ethylester, α-aminocaprolactam, 3-aminopiperidone (2), and 3-aminopyrrolidone (2) were acylated with 3-benzyloxy-4-methyl-2-nitrobenzoyl chloride. These compounds were catalytically hydrogenated to 3-hydroxy-4-methylanthraniloyl derivatives and then oxidized to actinocyl derivatives. In the course of these investigation, it was observed that dehydric cyclization occurs between carboxyl and amino group when 3-benzyloxy-4-methyl-2-nitrobenzoyl-L-proline is hydrogenated. Similar dehydric cyclization were observed in hydrogenation process of 3-benzyloxy-4-methyl-2-nitrobenzoyl-L-hydroxyproline and o-nitrobenzoyl-L-proline.

View full abstract

The reversibilities of the titration curves of 2-aminoethyl- and 3-aminopropylisothiuronium salts were discussed. The potentiometric titration was done at various titration speeds and at various temperatures. Though the titration curves of these two compounds showed different behaviors against the rate of alkali addition, it was confirmed that both compounds were transguanylated during the titration. The isothiuronium salt was ionized to the unstable conjugate base, which was in turn transguanylated rapidly to mercaptoalkylguanidine. In 2-aminoethylisothiuronium salt, however, the conjugate base was partly cyclized to 2-aminothiazoline. From the titration curves, the apparent ionization constants were determined graphically ; pK_a values at 25°of 2-aminoethyl- and 3-aminopropyl-isothiuronium salts were 7.5 and 8.6, respectively.

View full abstract

Mixed carbonic-carboxylic acid anhydrides, prepared in situ from carboxylic acids and ethyl chloroformate, were reduced with sodium borohydride in aqueous tetrahydrofuran to the corresponding alcohols in fair yields. Under the reaction condition examined, it was possible to reduce carboxyl group selectively to hydroxymethyl group in carboxylic acids having functional groups such as nitro-, cyano-, amido-, ester-group, and conjugated double bond. The general procedure for this reaction is given.

View full abstract

The steroidal components contained in the Rokko population of the D. tenuipes complex were inverstigated. From its aerial parts, one triterpene, one sterol and eight steroidal sapogenins were isolated. They were taraxerol, β-sitosterol, yamogenin, yonogenin, tokorogenin, diotigenin, recently isolated, three new sapogenins and an unknown steroidal compound. Two of the new sapogenins were 25L-epimers of yonogenin and tokorogenin, and named neoyonogenin and neotokorogenin, respectively. Another new sapogenin was a 25L-tetrahydroxysapogenin and named tenuipegenin. Besides these, diosgenin and stigmasterol were detected by infrared spectrum and gas chromatography, respectively. The steroidal sapogenins of this population were chiefly composed of 25L members. The coexistence of 25 D- and 25L-sapogenins in individual plants was also discussed.

View full abstract

The effect of 14 thiocyanato derivatives of purines and their ribonucleosides were compared with the effects of 6-purinethiol and 2-amino-6-purinethiol against transplanted sarcoma (NF-Sarcoma) in mice and the correlation was noted between antitumor activities and substituting position of thiocyanato group and other substituent groups on the purine ring. 6-Thiocyanatopurine, 2-amino-6-thiocyanatopurines and their ribonucleosides were demonstrated as the most active of the thiocyanato derivatives.

View full abstract

Nodosin, a new diterpenoid isolated from Isodon trichocarpus KUDO and I. Japonicus HARA, was converted to the keto lactone acetal X via several steps of reactions. The conversion made it possible to propose the structure II for nodosin. The remaining hydroxyl group proved to be located at C-11 and to have the β-configuration on the basis of a detailed NMR investigation. Thus, the structure and absolute configuration of nodosin were established as formula XIX.

View full abstract

The Bischler-Napieralski cyclizations of 2-(3, 4-dimethoxyphenethyl) hexahydro-Δ^{4, 5}-3 (2H)-isoquinolone (V) and a mixture of V and the Δ^{5, 10}-isomer, yielded 1, 2, 3, 4, 4a, 5, 7, 8-octahydro-benzo [g] 10, 11-dimethoxybenzo [4, 5-a] pyridocolinium chloride (VI) and the corresponding isomeric mixture (XI), respectively, both of which were dehydrogenated to yield the same product, 1, 2, 3, 4-tetrahydrobenzo [g] 10, 11-dimethoxybenzo [4, 5-a] pyridocolinium iodide (VII). Dihydrosempervirine (XVII) was easily synthesized in the similar manner.

View full abstract

Methylenation of catechols with methylene halides was found to be catalyzed more effectively by cupric oxide in dimethylformamide.

View full abstract

Ethyl 1-methyl-2-benzimidazolecarboxylate 3-oxide (XVII) was synthesized from 1-methyl-2-benzimidazolecarboxaldehyde oxime 3-oxide via the corresponding nitrile (III) and imido ester (XIII). Both reactions of III and XIII with potassium hydroxide gave 1-methyl-2-benzimidazolol 3-oxide. From III, 2-carboxamide (XI), 2-thiocarboxamide derivatives and 6-hydroxy-1-methyl-2-benzimidazolecarbonitrile were obtained. L-2-(6-Hydroxy-1-methyl-2-benzimidazolyl)-△²-thiazoline-4-carboxylic acid was synthesized from III, which has an analogous structure to firefly luciferin but it was inactive as far as light production was concerned. From XIII, 2-amidrazone, 2-tetrazole derivative and 1, 1'-dimethyl-2, 2'-bibenzimidazole 3-oxide were prepared. Hydrolysis of III and XIII with hydrochloric acid gave 1-methylbenzimidazole 3-oxide. The corresponding amide XI, acid hydrazide and hydroxamic acid were obtained from XVII. Reaction of XVII with piperidine did not give the corresponding amide but a mixture of 1-methylbenzimidazole 3-oxide and piperidine urethan. 3-(α, β-Dimethoxycarbonyl-β-hydroxyvinyl)-2-ethoxycarbonyl-1-methylbenzimidazolium betaine was prepared from XVII and dimethyl acetylenedicarboxylate.

View full abstract

3-Amino-3-deoxy-D-allouronic acid hydrochloride (VII) was synthesized. Barium 3-oxo-1, 2-O-isopropylidene-D-glucofuranuronate (IV) was converted into the corresponding phenylhydrazone (V) which was hydrogenated to give the 3-amino compound (VI). Acidic hydrolysis of VI gave VII crystalline. The oxime (IX) of methyl 5-O-acetyl-3-oxo-1, 2-O-isopropylidene-D-glucofuranuronate (VIII) was found to undergo stereospecific reduction with lithium aluminum hydride to give 3-amino-3-deoxy-D-allose derivative (IIIb¹⁴) predominantly. Displacement at C-3 of methyl 5-O-acetyl-3-O-methanesulfonyl-1, 2-O-isopropylidene-D-glucofuranuronate (Ib) with sodium azide and subsequent catalytic hydrogenation gave methyl 5-O-acetyl-3-amino-3-deoxy-1, 2-O-isopropylidene-D-allofuranuronate (IIb) in low yield.

View full abstract