A near-infrared spectrophotometric method was developed for the determination of allylisopropylacetureide and phenacetin in their pharmaceutical preparations containing allylisopropylacetureide, phenacetin, aminopyrin, isopropylantipyrine, and caffeine, which are difficult to determine at usual NaCl infrared region. Chloroform is chosen as solvent and the sample solution is placed in a quartz cell of 10 mm. light path. The key bands used for allylisopropylacetureide and phenacetin are 5042 and 4952 cm-1, respectively, and these components can be determined easily without interferences of aminopyrine. isopro-pylantipyrine, and caffeine. This method gave good results both in standard mixed samples and unknown samples, and the method is very useful for a routine analysis with simple operations.
Systematic examinations were made on the alkaloidal components of Pachysandra terminalis SIEB. et ZUCC. (Japanese name Fukki-so) (Buxaceae) and 27 kinds of new alkaloids were isolated in crystalline form. The alkaloids whose structure has been established to the present all belong to steroidal alkaloids of pregnane type.
Previously, the dissociation of O-glucuronides was made with mineral acid non-enzymatically, but it was found to be dissociated with l-ascorbic acid. In this case, the dissociation was promoted with cupric ion catalytically. It was recognized that the dissociation was effected by active hydrogen peroxide produced from l-ascorbic acid. Moreover, the dissociation occurred when hydrogen peroxide was added to O-glucuronides. In this case, metal ions Fe2+, Fe3+, Cu2+, Co2+, Mn2+, and Zn2+ promoted the reaction. The reaction was assumed to be the oxidative dissociation of O-glucuronides.
Application of cyanogen chloride and 1-phenyl-3-methyl-5-pyrazolone to chloropheniramine maleate results in reddish violet coloration and the solution has absorption maximum at 550 mμ. By using this coloration reaction, colorimetric determination of chloropheniramine maleate was examined and a sensitive method was established in which adverse effect of existing substances was minimized. By the use of this method, the usual substances compounded in ordinary cold cures such as sulpyrin, aminopyrine, acetylsalicylic acid, 4-hydroxyacetanilide, phenacetin, caffeine, guaiacol glycerol ether, methylephedrine hydrochloride, and dihydrocodeine phosphate would not interfere in the determination even if present in 75 volumes of chloropheniramine maleate, and noscapine in 15-fold amount. On the other hand, pyridoxine hydrochloride affects the determination even in 3-fold amount and riboflavine causes negative error if present in one-half the amount of chloropheniramine maleate. These interferences can be removed by extraction of chloropheniramine with petroleum ether in ammonia alkalinity. Concentration range of chloropheniramine maleate determinable by this method is 100∼500 μg./5 ml., and precision of measurement is σ^^^= 1.54% (n=6).
In order to synthesize cularicine (I), the dicarboxylic acid (II) was synthesized, though in a very poor yield, from the dialdehyde (IX) which was derived to azulactone (X), hydrolyzed, and treated with hydrogen peroxide. II was also obtained in a comparatively good yield by reduction of IX with sodium borohydride to the alcohol compound (XI) which was derived via the chloro-compound (XII) to the nitrile (XIII), and its hydrolysis. Cyclization of II by polyphosphoric acid and polyphosphoric acid ester did not materialize and synthesis of cularicine was not effected.
Isooctane solution and crystal of guaiazulene were irradiated with 102 to 108 r of γ-ray from cobalt-60 and their absorption spectra were measured in the ultraviolet region. The aqueous solution of sodium guaiazulene-3-sulfonate was also irradiated similarly and its spectra were measured. There was no general change in the absorption but it was found that the visible spectrum of the irradiated isooctane solution showed changes of arithmetical mean type of about 40 in the mean value of total absorption in the absorption ×103 value and about 12 in the fluorescence spectra, in the order of 10 irradiated dose. It was thereby considered that, in general, absorption values change in arithmetical or geometrical series up to a certain limit of the irradiation dose. The infrared ana NMR spectra of guaiazulene crystal irradiated with γ-ray showed practically no change from those of non -irradiated guaiazulene.
The leaves of Evodiopanax innovans NAKAI were extracted with methanol and the extract was treated as shown in Chart 1. Maltol and rhoifolin were isolated and identified. The latter was dissolved in ethanol containing 2% of sulfuric acid and boiled 20 minutes to give cosmosiin and rhamnose in a good yield (Chart 2).
The terrestrial portion of Dianthus superbus L. var. longicalycinus (MAXIM.) WILLIAMS (Japanese name Kawara-nadeshiko) (Caryophyllaceae) was extracted with methanol and the extract was examined by a thin-layer chromatography. Four kinds of saponin were detected and these were named dianthus-saponin A, B, C, and D in the descending order of Rf values. One of them was found to be a new saponin having gypsogenic acid as an aglycone and glucose as the sugar.
Following previous work on the partial syntheses of AB and CD rings in I and II, and synthesis of ABCD skeleton possessing a substituent that can be derived to the C-ring, possibility of synthesizing I and II by the condensation of AB and CD rings was examined. The Ullmann reaction of 6-bromo-2, 3-dimethyl-4-phenylpyridine (Vc) and 2-bromoquinoline (VIIa) afforded, through in a low yield, 2, 3-dimethyl-4-phenyl-6-(2-quinolyl)pyridine (VIII), with a by-product formation of a dipyridyl derivative (IX). For the synthesis of the ABCD skeleton, XVIII, obtained in a good yield from 2-cyanoquinoline, was hydrolyzed with alkali and then with acid to 2-acetylquinoline and this was submitted to the Claisen-Schmidt reaction with piperonal and vanillin. The condensation products (XVIb∼c) were condensed with cyanoacetamide in the presence of piperidine and the pyridone derivatives (XVIIb∼c) with the ABCD skeleton were finally obtained.
Following the previous work*2 on the syntheses on the partial structure of the anticancer antibiotic, streptonigrin (I), and its dihydrohexamethyl derivative (II), structure of the intermediate compound (IV) was examined through the NMR spectrum. It was thereby found that this is not the expected compound (IV) but is its isomer (XIX). In order to determine the structure of the intermediates from III to XIX, NMR spectra of various related compounds were compared and it was found that unexpected dibromo-derivative had been formed in the bromination of the pyridone compound (III).
Fusion reaction of methyl salicylate and secondary amines afforded salicylamide compounds in a low yield only in the case of 1, 2, 3, 4-tetrahydroisoquinoline (I) and piperidine, and the amide compound was not obtained in the case of 1, 2, 3, 4-tetrahydroquinoline (II), N-methylbenzylamine (III), N-methylaniline (IV), and diphenylamine (V), forming N-methylated tertiary amines as the main product. Further, when such tertiary amines were 2-methyl-1, 2, 3, 4-tetrahydroisoquinoline (VII) and N, N-dimethylbenzylamine, quaternary ammonium salicylate was also formed. When the secondary amine was a comparatively strong base like I, salicylate of I was also found to be formed as a by-product.
Phosphorus oxychloride employed as an efficient phosphorylating agent in the synthesis of nucleotides was found to be an excellent catalyst for the conversion of ribonucleosides to their 2', 3'-O-isopropylidene derivatives. 2', 3'-O-Isopropylidene was obtained in a high yield. This fact has led to the establishment of a novel, single-step conversion of ribonucleosides to 5'-ribonucleotides in a high yield using phosphorus oxychloride, acetone, and pyridine, without isolation of the 2', 3'-O-isopropylidene derivatives.
A very convenient route to obtain DCET (III) via B1 acetal was presented. 3-Acetyl-3- chloropropanol (VI) was converted into O-tetrahydropyranyl acetal (VII) and condensed with dithiocarbamic acid (IX) to give thiazolidinethione acetal (X) readily. Dehydration of X by SoCl2-pyridine gave SB1 acetal (XV) in a high yield. Oxidative desulfurization of XV in AcOH solution in the presence of AcONa afforded B1 acetal (XIV), which was easily separated as thiocyanate. XIV reacted with ClCOOC2H5 in NaOH solution to give CET acetal (XVII) in a high yield, and DCET was readily obtained from XVII by thd action of phosgene with subsequent treatment with ethanol. This method is considered to be very convenient in producing DCET industrially, because each step progresses by simple operation and in a high yield.
Both 2-(4-bromo-3-oxo-1-butenyl)-5-nitrofuran (III) and 2-(4, 4-dibromo-3-oxo-1-butenyl)- 5-nitrofuran (IV) were synthesized by bromination of 2-(3-oxo-1-butenyl)-5-nitrofuran (II) in acetic acid or chloroform, blowing off the formed hydrogen bromide by nitrogen gas stream. To avoid the formation of IV, diethyl 3-(5-nitro-2-furyl)acryloylmalonate (I) was brominated under the same conditions as described above, followed by acid catalyzed hydrolysis, and III was obtained with a small amount of its isomer, 2-(2-bromo-3-oxo-1-butenyl)-5 nitrofuran (VI). In these cases, the addition reaction of bromine or hydrogen bromide to the double bond was not observed. III was reacted with hydrochloric acid and acetic acid in the pre-sence of guanidine carbonate to give 2-(4-chloro-3-oxo-1-butenyl)-5-nitrofuran (X) and 2-(4-acetyloxy-3-oXo-1-butenyl)-5-nitrofuran (XI) respectively. Their antimicrobial activities were presented.
Sugar derivatives containing sulfur were screened for antitumor activity by using the ascites and solid type of Ehrlich carcinoma cells. The method is based on our previous report.9)β-D-Xylopyranosyl ethylxanthate (I) and β-D-mannopyranosyl ethylxanthate (II) showed a marked antitumor effect on ascites type of Ehrlich carcinoma cells. Some discussions are given about the position or sulfur in these sugars in view of their antitumor activity.
Reaction of p-(trimethylsilyl)- (IV) and m-(trimethylsilyl)chlorobenzene (V) with various electrophilic reagents was examined. Bromination, nitration with acetyl nitrate, and Friedel-Crafts acylation of IV respectively afforded p-bromo-chlorobenzene, p-chloro-nitrobenzene, and p-chloro-acylphenone. Nitration of V resulted in substitution of the chlorine in paraposition with a nitro group to produce 2-(trimethylsilyl)-4-chloro-nitrobenzene (VII), which was reduced to 2-(trimethylsilyl)-4-chloroaniline (VIII) and further decomposed by acid to p-chloroaniline. Bromination and Friedel-Crafts acylation of V do not result in substitution of the chlorine in para-position and desilylation occurs in meta-position to produce m-bromo-chlorobenzene and m-chloro-acylphenone. Such a reaction does not occur in other meta-substituted (trimethylsilyl)benzenes. It is assumed that such independence of the substituent position from the +M effect of the functional group and desilylation by electrophilic reagents occurring solely by the + I effect of the trimethylsilyl group would appear as the +M effect of the functional group becomes smaller.
Analgesic action and pharmacological properties of 1-(2-diethylaminoethyl)-2-(p-ethoxyphenylthio)benzimidazole monohydrochloride (I). I showed similar analgesic effect as morphine when tested by the pressure method and D'Amour-Smith method, but hypotensive and respiration inhibitive activities of I were stronger than those of morphine. Analgesic, hypotensive, and respiration inhibitory actions of I were antagonized by Levallorphan while I caused addiction in rats same as morphine. I also caused Straub's reaction in mice, same as morphine. In such a way, I has a morphine-like action and was proved to have pharmacological effects similar to narcotic analgesics in spite of the absence of any structural similarity.
1-(2-Diethylaminoethyl)-2-(p-ethoxyphenylthio)benzimidazole (I) is considered to be a morphine-like analgesic and its derivatives, 1-(diethylaminoalkyl)-2-(p-ethoxyphenylthio) benzimidazoles, were synthesized to test their analgesic effect by the pressure method. Except for the 1-(2-pyrrolidinoethyl)derivative showing better activities than I or morphine, other derivatives did not show much effect, such as 1-diethylaminomethyl, 3-diethylaminopropyl, 1-[2-(allylamino)ethyl], 1-(2-dialkylaminopropyl), and 1-(1-methyl-2-piperidinoethyl) derivatives. The allyl derivative did not show any antagonistic action against I or morphine. Some discussions were made on the central atom, basic nitrogen, and the flat aromatic portion in the molecules of I and its analogs.
In an earlier work, it was found that the treatment of 2-nitro-1-tetralone oxime (II) with polyphosphoric acid resulted in the formation of 1-oxo-4, 5-dihydro-1H-(1, 2, 4)-oxadiazolo-[4, 3-a]quinoline (IV) and 4, 5-dihydronaphtho[1, 2-c]furazan 3-oxide (V). In the anticipation that the same treatment of 2-nitro-1-indanone oxime (I) might produce the similar compounds (VI and VII) corresponding to those of II, I was treated with 20 volumes of polyphospholic acid by warming at 45∼50° for 40∼50 minutes but the majority of the substance became resinous. The liquid obtained after removal of the resinous substance was salted out and extracted with ethyl acetate, affording two kinds of substances in 15% yield. These products were identified as 2-oximino-4-oxoisocarbostyril (VIII) and 2-oximino-1-indanone (IX).
A quaternary protoberberine-type base, cyclanoline (II), was isolated from the tuber of Formosan Stephania tetrandra S. MOORE (Japanese name "Shima-hasunohakazura"), in addition to tetrandrine (Ia) and fangchinoline (Ib). The terrestrial portion of this plant also yielded Ia and Ib.
The leaves of Fagara ailanthoides ENGL. afforded pale yellow needles of m.p. 143∼144° in 0.001% yield, which was identified with xanthotoxin. Diosmin, pale yellow crystals, m.p. 276°, was obtained from the pericarp of F. ailanthoides ENGL. and F. shinifolia ENGL. in 9.2% and 7.5% yields. Scopoletin, pale yellow needles of m.p. 195°, was obtained from the root bark of F. schinifolia ENGL. in 0.01% yield.
Decarboxylation of N, N-dimethyl-L-leucine and N, N-dimethyl-L-phenylalanine by heating at 240∼280° in diphenylamine or tetralin respectively afforded N, N-dimethylisopentylamine (I) in 20% yield and N, N-dimethyl -β-phenethylamine (II) in 27.5% yield. The same treatment of N, N-dimethyl-DL-methionine in diphenylamine afforded N, N-dimethyl-3-methylthio-propylamine (III) in 15% yield. Decarboxylation of N, N-dimethyl-L-leucine had been considered impossible by Chatelus3) and the fact that I was obtained even in 20% yield is worthy of note.