When isotetrandrine is reacted by metallic sodium in liquid ammonia, it is bisected into two bases of l-1-(4′-methoxybenzyl)-6, 7-dimethoxy-N-methyl-1, 2, 3, 4-tetrahydroisoquinoline (II) and d-1-(4′-hydroxybenzyl)-6-methoxy-7-hydroxy-N-methyl-1, 2, 3, 4-tetrahydroisoquinoline (III). Therefore, it has been determined that the structure of isotetrandrine and the steric configuration of the two asymmetric centers in the isotetrandrine molecule should be represented by formula (I). It was clarified that, as the consequence of reëxamination of the so-called trimethylcoclaurine of m.p. 202-203°, it is not O, O-dimethyl-N-methyl-coclaurine (II) as described in the literature, but should be corrected as O, O-dimethyl-coclaurine (VI).
When tetrandrine is reacted with metallic sodium in liquid ammonia, exactly the same cleavage takes place as in the case of isotetrandrine; thus d-1-(4′-methoxybenzyl)-6, 7-dimethoxy-N-methyl-1, 2, 3, 4-tetrahydroisoquinoline (II) and d-1-(4′-hydroxybenzyl)-6-methoxy-7-hydroxy-N-methyl-1, 2, 3, 4-tetrahydroisoquinoline (III) are obtained. Therefore, it has been positively clarified that the structure of tetrandrine is as described by formula (1), and the two asymmetric centers in the molecule of tetrandrine are both in d-form.
When cycleanine (I) is reacted with metallic sodium in liquid ammonia, it is bisected into l-1-(4′-hydroxybenzyl)-6, 7-dimethoxyl-N-methyl-1, 2, 3, 4-tetrahydroisoquinoline (l-armepavine) (II). Therefore, it has been confirmed that the structure of cycleanine and the steric configuration of the two asymmetric centers in the molecule must be represented by (I).
The authors synthesized dl-coclaurine hydrochloride from β-(3-methoxy-4-benzyloxy)-phenylethylamine (III) and 4-benzyloxyphenylacetyl chloride (IV, R=-CH2C6H5). Comparison of the substance here obtained with the one Finkelstein recently prepared showed that both gave identical data.
1. A compound obtained from the fruits of Juniperus rigida Sieb. et Zucc. and Juniperus conferta Parl. was found to have a remarkable antibacterial activity against Staphylococcus aureus. It could prevent the growth of the test organism in a dilution of 1:12, 800 and 1:51, 200 in broth and Knight's synthetic medium, respectively. 2. The antibacterial compound seems to be a diterpenic acid having the molecular formula C20H30O2 with optical activity [α]D23=+11°.
N-Methyl-4-aminopiperidine was prepared through the following three different methods: (1) The ring closure method starting with β, β′-dicarbomethoxy-diethyl-methylamine, (2) the treatment of N-methyl-4-pyridone-imine with sodium in boiling isoamyl alcohol, and (3) the catalytic hydrogenation of 4-acetaminopyridine-N-methiodide. The identities were established by m.p. and mixed m.p. of their dipicrates. N-Methyl-4-pyridone-imine was hardly susceptible to catalytic hydrogenation in the usual solvents. 4-Nitropyridine-N-oxide and 4-acetaminopyridine-N-oxide were also resistant to the similar treatment, but their hydrogenations were effected in glacial acetic acid-acetic anhydride mixture. It was also clarified that acetylation of 4-aminopyridine proceeded mostly towards 4-acetaminopyridine, because this formed an N-methiodide, which was converted into N-methyl-4-pyridone-imine on hydrolysis, and the N-methiodide was led to N-methyl-4-aminopiperidine by catalytic hydrogenation. 2-Aminopyridine showed the similar behavior. When the benzoylation was followed by treatment with methyl iodide, an N-methiodide was formed, and on hydrolysis, this was converted to N-methyl-2-pyridone-imine.
1) Dehydrobromination of 2, 6-dibromo-4, 4-dimethylcyclohexanone with sodium acetate gave 4, 4-dimethyl-2-acetoxy-Δ2-cyclohexenone and 4, 4-dimethylcyclohexadione (1, 2). 2) Dehydrobromination of 2, 6-dibromo-4, 4-dimethylcyclohexanone with quinoline gave 4, 4-dimethylcyclohexadienone, 2-bromo-4, 4-dimethyl-Δ2-cyclohexenone, and 1, 2-dimethyl-4-hydroxybenzene. 3) The position of bromine atoms in 2, 6-dibromo-4, 4-dimethylcyclohexanone was discussed.
From the bark of Magnolia obovata, Thunb., belonging to the Magnoliaceae, a new alkaloid, named magnocurarine, was isolated, and its chemical structure has been determined as N-methylcoclaurine methyl hydroxide (II).
The authors synthesized 3, 4-dimethoxydiphenyl ether-6, 4′-dicarboxylic acid (XI, R=H), m.p. 285°, and its dimethyl ester (XI, R=CH3), m.p. 132.5-133°, from methyl 6-bromoveratrate (IX) and methyl 4-hydroxybenzoate (X) by Ullmann's reaction. The data of these substances were found to be quite identical with those of magnolamic acid, m.p. 280-281°, and its dimethyl ester, m.p. 131-132°. According to these experimental results and from the view-point of the biogenesis of biscoclaurine alkaloids, the presumption of formula (VII) for magnolamine seems to be most rational.
Die Nitrierung von Chinaldin-N-oxyd wurde unter Berücksichtigung der Reaktionstemperatur durchgeführt. Chinaldin-N-oxyd ist gegen die Nitrierung reaktiver als das Chinolin-N-oxyd, obwohl der Reaktionsverlauf analog ist. Es wird bei niederer Temperatur hauptsächlich an C5 und C8 nitriert. Gegen 50° beginnt die Reaktivität an C4 rasch zu zunehmen, und bei über 100° nimmt die Ausbeute des 4-Nitrochinaldin-N-oxydes infolge der Deoxydation der N-Oxyd-Gruppe wieder ab, unter gleichzeitiger Bildung von Chinaldin sowie seinem 5- und 8-Nitroderivat. Bei niederer Temperatur wurde auch die Entstehung von 4, 8- und 4, 5-Dinitrochinaldin-N-oxyd bemerkt, wenn die Reaktionsdauer ausgedehnt wurde. Die beiden letzteren wurden auch durch die analoge Nitrierung von 8- bzw. 5-Nitrochinaldin-N-oxyd erhalten.
Durch eine Reihe von Versuchen über die Einwirkung von Phosphortribromid auf das 4-Nitrochinolin-N-oxyd wurde es festgestellt, dass es bei unter 15° in das 4-Nitrochinolin mit fast theoretischer Ausbeute übergeht und bei über 30° das 4-Bromchinolin nebenbei entsteht, und zwar mit zunehmender Menge, mit zunehmender Temperatur, Die chemischen Umsetzungen von 4-Nitrochinolin wurden mit denselben seines N-Oxydes vergleichend untersucht.
1) 4-Oxypyridin- und 4-Alkoxypyridin-N-oxyd werden durch die Druckhydrierung in alkoholischer Lösung je in das entsprechende Tertiäramin sehr glatt, und zwar mit guter Ausbeute reduziert, während sie gegen die katalytische Reduktion in neutralem Medium unter normalem Druck einen merklichen Widerstand zeigen. 2) 4-Alkoxypyridin, vorzüglich 4-Methoxypyridin, wird bei der Druckhydrierung nur dann von einer Umlagerung begleitet, wenn entweder ein Komplexsalz, welches aus dem 4-Alkoxypyridin und dem Metallchlorid leicht zur Entstehung kommt, oder wenn es unter den in der Zwischenstufe entstehenden Bedingungen reduziert wird, wobei N-Alkyl-4-pyridon als das Hauptprodukt neben dem 4-Pyridon gebildet wird.
N-Methyl-4-pyridon wird durch die Druckhydrierung in Methanol mittels Raney-Nickels schon bei tiefer Temp. (80-100°) zu N-Methyl-4-oxypiperidin reduziert, während das 4-Pyridon und 4-Methoxypyridin einer derartigen Reduktion widerstehen. Die günstigste Temp. zur Herstellung von N-methyl-4-oxypiperidin liegt zwischen 150-160°. Ueber 160° wird das Letztere teilweise zu N-Methyl-piperidin reduktiv zersetzt.
1) 3-Acyl-2, 4-dihydroxyquinolines were synthesized by the Friedel-Crafts reaction of 2, 4-dihydroxyquinoline, and similarly, N-alkyl-3-acyl-4-hydroxyquinolones-(2) by the same procedure of N-alkyl-4-hydroxyquinolone-(2). Some of them were also prepared by the cyclization method to confirm the chemical structures of the products obtained by the Friedel-Crafts reaction. 2) 3-Acetyl and 3-benzoyl derivatives of both 2, 4-dihydroxyquinoline and N-alkyl-4-hydroxyquinolone-(2) were also derived from their acetates and benzoates by the Fries rearrangement. 3) 3-Formyl derivatives were prepared by the Reimer-Tiemann reaction. 4) The ultraviolet absorption spectra of these synthetic compounds and of the related substances were examined for the identification of their chemical structures. 5) Most of these acylated compounds were found to be less active against Staph. aureus in vitro than 3-acyl-4-hydroxycoumarins. 6) N-Methyl-3-acyl-4-hydroxyquinolones-(2) were found to have a slight tendency to increase their antimicrobial activities with the elongation of their carbonyl side chains.
The mechanism of inversion of the stereochemical configurations of santonin, β-santonin and desmotroposantonins was discussed. The absolute configurations of these compounds was confirmed by the crystallographic method and a comparison of the stability of the lactone linkage.
Using the high frequency titrimeter, the change in test solution in the titration could be followed through reading the observed change in plate current, Im, and the complex formation in test solution could be determined. From the results obtained, the general considerations of its application are summarized as follows; 1. The titration should be carried out in dilute solution since the reproducibility and the sensitivity are good. 2. Good reproducibility and sensitivity were obtained in the titration of coordinate compound with metallic salt. There was no difference in its results either with or without stirring. 3. To calculate the equivalence point, an extrapolation of the curves is necessary except in the case in which the electric current Im continuously increases or decreases beyond the breaking point. 4. If the decrease in Im beyond the breaking point is observed, in the titration of metallic salt with coordinate compound, Im increases when the coordinate compound is titrated with metallic salt. Thus, between the order of the titration and the increase or decrease in Im, there exists the contrary relationship. However, there are exceptions to this.
By means of the high frequency titration, the formation of metallic complex salts of pyridine, hexamine, ethylenediamine and α, α′-bipyridyl was studied. The results are as follows: 1) In the pyridine complex salts of copper, nickel or zinc, the breaking points in the titration curve are approximately at 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:1.5 and 1:3 for that of calcium, and 1:2, 1:3, 1:4 and 1:5 for that of lithium. 2) The curves for hexamine complex salts of nickel, copper or zinc have the breaking points approximately at 1:0.5, 1:1, 1:2 and 1:3. 3) The titration curves for ethylenediamine complex salts of copper, nickel or cadmium are complicated, not showing good reproducibility. However, the breaking points are approximately at 1:1, (1:1.5), 1:2, (1:2.5), 1:3 and (1:5). 4) The titration curves for α, α′-bipyridyl complex of nikel, copper, zinc, iron or manganese have the breaking points approximately at 1:1, 1:2 and 1:3. However, the titration curve for complex salts of iron and manganese, the breaking point 1:1.4 is marked unless it is extrapolated.
Using the high frequency titrimeter, the titrations of α- and β-naphthylamine, m- and p-phenylenediamine, picric acid, picrolonic acid and Titan yellow with various metallic salts were carried out. The results obtained are as follows; 1) The titration of α- and β-naphthylamine with cadmium nitrate or cobalt nitrate, the breaking points were approximately at 1:1 and 1:2. 2) The titration of m- and p-phenylenediamine with copper nitrate or ferrous sulfate, the breaking points were approximately at 1:1 and 1:2. 3) In the titration curve of p-phenylenediamine with magnesium nitrate, strontium nitrate, barium chloride or cadmium nitrate, there were two breaking points, approximately at 1:1 and 1:2. 4) In the titration curve of picric acid with nickel nitrate, copper nitrate, zinc nitrate, lead nitrate, strontium nitrate, mercuric chloride or silver nitrate, the breaking points were approximately at (1:1) and 1:2. In the titration curve of HgCl2-picric acid complex salt, the breaking point was not clear and its sensitivity was very slight. 5) The sensitivity in titrating picrolonic acid with calcium chloride, lead nitrate or copper nitrate was slight. The breaking points were approximately at 1:1 and 1:2. 6) The breaking point in titrating Titan yellow with cadmium chloride or magnesium nitrate was approximately at 1:1. Another unclear point was approximately at 1:2.
The high frequency titration was carried out in the formation of some inner complex salts. The results obtained are summarized as follows: 1) In the titration curves for dimethylglyoxime complex salt of nickel, copper or zinc, the breaking points were approximately at 1:1 and 1:2. The breaking point 1:3 is not clear, and therefore, doubt exists as to the existence of a new compound. 2) In the titration curves of salicylaldoxime complex salt of copper, nickel or lead, the breaking points are approximately at 1:1 and 1:2. 3) In the titration curves of cupferron complex salts, the breaking point is approximately at 1:2 for copper or strontium complex, approximately at 1:3 for aluminum complex. 4) In the titration curve of nitroso-R-salt of cobalt, the breaking point is approximately at 1:2.
By means of the high frequency titration, the change in titrating protein solution with various ammin-complex salts of cobalt and chromium was observed. 1) In all titration curves, one common breaking point, 25-35×10-5 equiv., was marked, irrespective of the valence, the variety of the central metal or coordinate molecule of complex salts. Besides the common breaking point above, the breaking point, 10×10-5 equiv., for Luteo, Roseo and Diroseo complex, 58×10-5 equiv., for Xantho complex was marked. 2) The change in Im in titrating with non-electric complex [Co(NH3)3(NO2)3] is almost linear and is similar to that of adding this complex to water. It seems that this is due to the change in its dipole content. 3) The equivalence of complex ion combined with 1g. of egg albumin is 35-40×10-5 equiv. and that obtained by high frequency chemical analysis is a little less.
Die Nitrierung von Benzo-(h)-chinolin wurde einer weiteren Prüfung unterworfen. Die frühere Beschreibung hierüber wurde zuerst korrigiert, dass das Mononitroderivat B vom Schmp. 166.5° kein einheitliches Produkt darstellt, sondern ein Gemisch aus 7-Nitroderivat und 5, 7-Dinitroderivat. Die Entstehung von 10-Nitroderivat wurde niemals bemerkt. Es soll auch berichtigt werden, dass das Chinolinochinolin aus dem B ein Gemisch aus dem Chinolino-(7, 8:8′, 7′)-chinolin und seinem Monohydroxyderivat ist. Bei der Nitrierung von Benzo-(h)-chinolin unter energischerer Bedingung wurden 5, 7-, 6, 7-Dinitrobenzo-(h)-chinolin und ferner drei Dinitroderivate vom Schmp. 272°, 206° und 235° erhalten.
For the purpose of biological assessment an amino-hydrobenzoquinolicine mentioned in the title and its N-dimethyl derivative were synthesized. β-3, 4-Methylenedioxy-phenylethyl bromide was heated with ethyl isonicotinate to form a quarternary bromide (I), which was then oxidized to the corresponding pyridone carboxylic acid (II) by the usual method. Its reduction product, the piperidone carboxylic acid (IV), was then cyclized and the product was treated with alcohol, giving carbethoxy-benzoquinolicinium salt (V), which was then reduced to hydrobenzoquinolicine (VI). Modified Curtius degradation was then applied to (VI), furnishing the final product (VII). Its N-dimethyl derivative was also prepared.