1-(p-Hydroxyphenyl)-3-dimethylamino-1-butanol (Ia) and 1-(3, 4-dihydroxyphenyl)-4-dimethylamino-1-butanol (II) were synthesized in order to examine their pharmacological action on autonomous nerve system. Reaction of dimethylamine with 4′-benzyloxyphenylcrotonophenone (Vc) gave 3-dimethylamino-4′-benzyloxybutyrophenone (VIc), which was reduced with lithium aluminum hydride to 1-(p-benzyloxyphenyl)-3-dimethylamino-1-butanol (Ic). Hydrochloride of Ic was obtained in two kinds of crystals: α-Ic hydrochloride, m.p. 164-164.5° (free base, α-Ic, m.p. 63-63.5°), and β-Ic hydrochloride, m.p. 157-158° (free base, β-Ic, m.p. 89.5-90°). Hydrogenolysis of both these free bases gave the corresponding 1-(p-hydroxyphenyl)-3-dimethylamino-1-butanol (Ia), α-Ia, m.p. 131-132°, and β-Ia, m.p. 122-123°. These are diastereomers. II was prepared by the catalytic reduction over platinum oxide of 4-dimethylamino-3′, 4′-dihydroxybutyrophenone (IX), obtained by the Friedel-Crafts reaction between catechol and 4-dimethylaminobutyryl chloride.
Syntheses of 2-naphthalenealkylamine derivatives, whose carbon number (n) of the alkyl group was varied from n=0-7 and n=10 (IIIa-XIa), and their N, N-dimethyl derivatives (IIIb-XIb) as well as their methiodide (IIIc-XIc) were carried out in order to examine their pharmacological activities. Anti-acetylcholine activities and anti-histamine activities were tested according to the Magnus method. Both activities showed a tendency to strengthen as the carbon number of alkyl group increased. However, the anti-acetylcholine activities of primary amine, whose n is 10, was observed to be a little lower than that of the amine of n=7. As to the anti-histamine activities, dimethylamino derivative of n=2 was found to be the strongest, that of 3 and 4 were weaker and it became stronger as the carbon number increased. The activities of methiodide of n=1 was a little stronger than that of n=2 in both activities. As to the blood pressure activities of primary amines, n=0 showed depression and n=1-4 showed, after a little depression, a rise type, whose degree was observed to be the maximum with n=2 and later weakened to a depress type. Dimethyl compounds were depressive andmethiodide showed usually a continuous rise, after the depression.
N-Alkyl (or Aralkyl) derivatives of N-methyl-2-naphthaleneëthylamine (Ia) and N-methyl-2-naphthalenepropylamine (IIa) and their methiodides were synthesized. Tertiary amines (I and II, b-j) obtained and their methiodides were tested for atropine- and papaverine-like activities by the Magnus method, and the relationships between the structures and pharmacological activities were discussed.
A mechanism of color reaction of sodium 1, 2-naphthoquinone-4-sulfonate with either o-cresol or resorcinol was investigated by isolating reaction products. Reaction of sodium 1, 2-naphthoquinone-4-sulfonate with either o-cresol or resorcinol, in the presence of sodium hydroxide and pyridine, produced 3-methyl-3′-hydroxy-5′, 6′-benzo-4, 4′-diphenoquinone (II) from o-cresol and 2, 3′-dihydroxy-5′, 6′-benzo-4, 4′-diphenoquinone (III) from resorcinol, respectively. The absorption curves of II and III in alkaline solution are nearly coincident with that of the colored solution produced by 1, 2-naphthoquinone-4-sulfonate and either o-cresol or resorcinol. Therefore, the reaction mechanism of the coloration is considered that sodium 1, 2-naphthoquinone-4-sulfonate attacked at p-position of phenol initially as an electrophilic reagent to form addition product of 1, 2-naphthoquinone-4-sulfonate tentatively, and then desulfonation afforded either II or III, which showed coloration in alkali by dissociation.
Colorless leaflet crystal of m.p. 280-282° (decomp.), C5H9O4N, [α]D ±0° (c=2.00, 0.5N HCl) was isolated from Chondria armata (Kützing) Okamura and it was identified to be 3-aminogultaric acid. It was considered to be of great interest that 3-aminoglutaric acid was isolated firstly from natural products.
Free amino acids of Laminaria angustata (Jap. Name Mitsuishi Kombu) were determined by amino acid analyzer quantitatively, and glutamic acid, aspartic acid, alanine and proline were found in a larger amount. After an purification of 19 kinds of water extracts from seaweeds through Amberlite IR-120 and IRC-410, laminine content was determined by ion-exchange chromatography of Amberlite IRC-50. As it is strong alkali, laminine was not completely eluted from Amberlite IR-120, giving such a rate of recovery, in 64-70%. The results of the determination were shown in Table II. Laminine was isolated and identified also from Ecklonia cava (Jap. Name Kajime).
After an cultivation of drug-resistant E. coli on the synthetic medium which containes the drug, the content of the drug in the filtrate of the culture medium was determined chemically, and it was found that three kinds of antibiotics such as dihydrostreptomycin, chloramphenicol and tetracycline were decomposed by microorganisms strongly. The decomposition reaction of the drug is simultaneously an inactivation which was considered to be intracellular. However, sulfisomidine was found to be remained almost undecomposed by microorganisms. As to the three kinds of antibiotics, an ability of drug decomposition by microorganisms is considered to be one of the possible factors in the drug-resistant mechanism of E. coli. However, another mechanism should be considered in the case of sulfa-drugs.
Reactions of diketene with acid-hydrazides RCONHNH2 (II), where R is phenyl (IIa), p-chlorophenyl (IIb), p-methoxyphenyl (IIc), 2-pyridyl (IId) and 3-pyridyl (IIe), afford their acetoacetates (IIIa-e), respectively. III is easily hydrolized to give diacyl hydrazines (Ia-e) in a good yield.
The lactone compound, prepared by the Baeyer-Villiger reaction of 3-oxo-steroids is reported to give 3a-oxa compound solely. However, it was certified to be a mixture of 3-oxo-3a-oxa-A-homo compound and 3-oxo-2a-oxa-A-homo compound in a ratio of either 1:1 or 3:1, and therefore in this reaction any specific course of oxidation was not found by the following methods. The lactone compound, derived from five kinds of 3-oxo-steroids having 5α and 5β configuration, was opened in its ring and then oxidized to secodicarboxylic acids, followed by partial esterification at room temperature in 2% hydrochloric acid containing methanol and finally diester and semiester were quantitatively separated. It was identified that the former was 2, 3-secoic acid ester and the latter 3, 4-secoic acid ester. At the same time, several 2, 3- and 3, 4-secodicarboxylic acid derivatives were synthesized.
Hamaudol, C15H16O5, a constituent of the roots of Angelica japonica, has been shown to be a derivative of 2-methyl-5-hydroxychromone. On treating with p-toluenesulfonic acid, hamaudol gave two isomeric dehydration products, C15H14O4, one of which was identical with the anhydrovisamminol obtained by Schmid from visamminol, being an isomer however, it may not be identical with hamaudel. These findings suggested two possible structures, Ia and Ib, and the formula (Ib) was confirmed in a complete agrrement with hamaudol by its nuclear magnetic resonance spectrum.
When bromine was reacted to aromatic N-oxides in acetic anhydride, an introduction of bromine was taken place at the β-position or an equal position. Quinoline 1-oxide, pyridine 1-oxide, isoquinoline 2-oxide and 4- or 2-quinolinol 1-oxide produced 3, 6-dibromoquinoline 1-oxide, 3, 5-dibromopyridine 1-oxide, 4-bromoisoquinoline 2-oxide, 3-bromo-4-quinolinol 1-oxide and 6-bromo-2-quinolinol 1-oxide, respectively. Some considerations were given to the mechanism of this reaction.
In connection with the explanation of carcinogenic mechanism of 4-nitroquinoline 1-oxide, a strong carcinogenic substance, free radical reactions of 4-nitroquinoline 1-oxide and its related compounds were studied and a radical deoxygenation reaction was observed, being common in hetelocyclic N-oxide.
In connection with the carcinogenic mechanism of 4-nitroquinoline 1-oxide (4 NQO), 4-hydroxyaminoquinoline 1-oxide was led to 4, 4′-azodiquinoline 1, 1′-dioxide, being confirmed a production of 4-nitroso derivatives as an intermediate, and finally 4-phenylazoquinoline 1-oxide was synthesized.
Lipid component, extracted from dried cells of Torulopsis utilis was examined by means of chromatography. It was found that lipid content in dried cells was 3% and this lipid consisted mainly of phospholipid (84%), which was largely composed of lecithin, phosphatidylethanolamine and lysolecithin, however neutral lipids are formed mainly of free fatty acid, triglyceride and sterol. Analysis of the fatty acid composition of the isolated lipid fractions by gas-liquid chromatography showed that acid neutral lipids and phospholipids contained mainly linoleic acid, oleic acid and palmitic acid, while free fatty acid fraction had a very low content of linoleic acid. The lysolecithin fraction contained considerably larger amounts of linoleic acid than the other lipid fractions.
Seven kinds of basic crystals were isolated from Asimina triloba DUNAL. (paw-paw), cultivated in Japan. (Table I) Among them, asimilobine, C17H17O2N, m.p. 177-179°, [α]D -213° (CHCl3) was found to be a new base and the structure was certified to be the secondary aporphine type phenolic base, IIa.
From Chondria armata (KüTZING) OKAMURA, besides such an anthelmintic component as domoic acid, D-aspartic acid and L-citrulline, it was established that a newly isolated hypoxanthine, C5H4ON4⋅H2O, m.p. >300°, C5H4ON4⋅HCl, m.p. >300°, L-glutamic acid, sodium mannosidoglycerate, m.p. 264° (decomp.) and also succinic acid. It seems to be interesting to report that optically different type of compounds such as D-aspartic acid and L-glutamic acid were isolated from the same plant. It is supposed to be the first example that hypoxanthine was separated from seaweeds.