As are known by various sorts of the representative methylene type the bifunctional carbons, which signify the carbons linking two heterofunctional groups, have proved to furnish characteristic reactivities. That is to say, they can undergo easy substitution of their one-side group and receive insertion of unsatureted spieces into their one-side bond. The aim of author's investigation in this field was to develop basic reactions as well as new reagents which are useful for practicing organic chemists. This article is to review the work in this laboratory, which is constituted of numerous new reactions involving reduction, substitution, carbon-carbon bond formation, rearrangement, insertion, 1, 3-dipolar cycloaddition and so on, with development of new reagents such as formic acid-triethylamine azeotrope as a reducing agent, diazoalkane-generating agent and aromatic diazotategenerating agent. Application of the reactions to the syntheses of some physiologically active compounds is also briefly summarized.
We have investigated the alkaloidal constituents of the roots of Aconitum ibukiense NAKAI cellected at Mt. Ryosen (Shiga Pref.). In addition to the known twelve compounds i.e. mesaconitine, hypaconitine, aconitine, deoxyaconitine, 14-dehydrobrowniine, 14-dehydrodelcosine, delcosine, takaonine, neoline, 15-α-hydroxyneoline, senbusine A, and ignavine, four new bases, i.e. ibukinamine, ryosenamine, ryosenaminol, and 9-hydroxynominine, were isolated. The structures of ibukinamine, ryosenamine, and ryosenaminol were established to be 2, 3-dehydro-6-O-demethyldelcosine, 1-deoxyhypognavine, and 1-deoxyhypognavinol, respectively, by the spectroscopic evidence and by the X-ray crystallographic analyses. The structure of 9-hydroxynominine was deduced by the spectroscopic evidence.
3-(3', 5'-Dicholorosalicyloyl)-2, 5-dichloropyrrole (3) and 3-(3', 5'-dichlorosalicyloyl)-2, 4, 5-trichloropyrrole (4) was synthesized as isomers of pyrrolomycins C (1) and D (2). In order to synthesize 3-(3', 5'-dichlorosalicyloyl) pyrrole (5) which was chosen as a synthetic intermediate of 3 and 4, Friedel-Crafts acylation was carried out by the new method reported by Rokach et al. But, a major product of this reaction was 2-(3', 5'-dichlorosalicyloyl) pyrrole, an α-isomer corresponding to 5. Then, effects of acyl chlorides and Lewis acids on Friedel-Crafts acylation were studied in detail. When benzoyl, m-nitrobenzoyl and p-methoxybenzoyl chlorides reacted with N-benzenesulfonylpyrrole (6) by using anhydrous AlCl3 as a catalyser, substitution to β-position on pyrrole ring of 6 occurred predominantly. However, in the case of the use of anhydrous SnCl4 as a catalyser in this reaction, ratio of substitution to α-position increased. On the other hand, when 3, 5-dichloro-2-methoxybenzoyl chloride reacted with 6 in the presence of anhydrous AlCl3, substitution to α-position occurred mainly, and in the presence of anhydrous SnCl4, substitution to α-position further increased. Consequently, 3 and 4 were prepared from 6 by chlorination according to the Friedel-Crafts acylation reaction. Comparison of the antimicrobial activities of 3 and 4 with those of 1 and 2 revealed that 3 was equally active as 2 against Gram positive bacteria and that 3 and 4 were more active against some fungi than 1 and 2. However, the activities of 3 and 4 against Gram-negative bacteria were lower than those of 2.
New saponins, named lucyosides A (1), B (2), C (3), D (4), E (5), F (6), G (7), H (8), besides known ginsenosides-Re (9) and -Rg1 (10), were isolated from herb of Luffa cylindrica ROEM.. On methanolysis 1, 2, 3, 5, 7 and 8 yielded methyl 21β-hydroxyhederagenin (11), arjunolic acid (12), methyl machaerinate (13), hederagenin (14), maslinic acid (15) and oleanolic acid (17), respectively. The structures of 1-8 were elucidated mainly mass, 13C-nuclear magnetic resonance and 1H-nuclear magnetic resonance spectroscopy.
A kind of rhizome named "tepas terbang, " a folk medicine for vermifuge, of 'orang asli' collected in Pasoh Forest Reserve, Negri Sembilan, West Malaysia in 1971, was cultivated in the greenhouse belonging to Faculty of Pharmaceutical sciences, Kyoto University and identified as Hedychium longicornutum GRIFF. ex BAKER, Zingiberaceae, after coming into bloom in 1974. The inner structure of root and rhizome of the cultivated sample was examined in comparison with those of two species, H. chrysoleucum HOOK. and H. coronarium KOENIG, which had the same habitat as the sample. These three species were distinguished one another in the inner structure of the part used as medicine.
Histological study of marketed cinnamon bark produced in Viet-Nam was carried out for the determination of the botanical name in comparison with the bark specimens at several levels in three trees of Cinnamomum cassia PRESL collected in Indonesia. Twenty-nine samples of bark named Viet-Nam, Saigon and Annan cinnamon etc. were examined and classified into 6 types, i.e. A-I, A-II, A-III, B, C and D. The characteristics of these types were as follows : crystal was needles in types of A-group and B, sometimes in bundle, and prism in types of C and D. The difference in each type was the kinds and the amount of mechanical tissue such as stone cell ring and group, bast fibre, two sort of sclerenchyma, U- and O-form cell, and also the amount of oil cell. In addition the thickness of cell wall of parenchyma in secondary cortex was different. (see Table III) The types of A-group was identified as C. cassia PRESL, and the type of B was the same species as that of A-group, a cultivated form, as the result of histology and a survey of literatures concerned, though it has been suggested C. loureirii NEES and/or C. obtusifolium NEES. The types of C and D have not been identified yet.
The fluorescent coumarin derivatives of soyasaponin I (1), II (2), III (3), A1 (4), and A2 (5) were examined by high performance liquid chromatography (HPLC) and the quantitative determination method for soyasaponin I (1), II (2)+III (3), A1 (4), and A2 (5) by HPLC has been developed. By means of this HPLC method, the respective soyasaponin contents in various kinds of soybeans and soybean products have been clarified.
Kinetic analysis of thermal decomposition was carried out by using differential scanning calorimetry, derivative thermogravimetry, and thermogravimetry. 1) The thermal decomposition mechanism could be estimated by measuring the residual fraction (Cm) at a temperature when decomposition rate was maximum. The Cm was characteristic of reaction mechanism. 2) The activation energy could be estimated by measuring the difference between temperatures (Td) of maximum decomposition rate at different heating rates, or measuring the Td when the crystals decomposed to a certain fraction at different heating rates. The Td was independent of reaction mechanism.
A simple and rapid high performance liquid chromatographic (HPLC) procedure was established for the quantitative determination of dexamethasone (DM) in chinese medicine. DM was extracted with acetonitrile from chinese medicine, cleaned up by the use of a Sep-Pak C18 cartridge and determined by HPLC. DM was separated with a mobile phase of acetonitrile-water (33 : 67) on μ Bondapak C18 column. Acetaminophen (AA), bucetin (BC), phenylbutazone (PB) and indomethacin (IM) was extracted with chloroformacetone (1 : 1) from chinese medicine and determined by gas chromatography with 2% OV-17 column. DM, AA, BC, PB and IM from "Kyofushitsugan" and DM, PB and IM from "Tsuifutokotsugan" were detected as illegally enriched synthetic drugs.
Matrine and oxymatrine, major components of Sophora flavescens, were previously reported to have a protective effect on restraint and water immersion stress ulcer in mice. Oxymatrine inhibits the formation of some experimental gastric ulcers, pylorus ligation ulcer and indomethacin ulcer, which are considered to relate to acid secretion. Oxymatrine decreases acid secretion in Shay's rats and inhibits gastric motility induced by restraint and water immersion stress when administered intraduodenally. These results suggest that the protective effect of oxymatrine on stress ulcer is possibly due to a decrease of acid secretion and inhibition of gastric motility. In spite of its weak inhibition of gastric acid secretion, intravenous injection of matrine is rather effective for stress ulcer. Matrine exhibits the inhibition of writhing induced by acetic acid, prolongation of sleeping time induced by pentobarbital, hypothermia and inhibition of locomotor activity induced by methamphetamine. Matrine (i.v.) also inhibits gastric motility induced by restraint and water immersion stress. These results suggest that protective effect of matrine on stress ulcer is possibly related to the effect on the central nervous system.
The Raney nickel desulfurization of 7-aminodeacetoxycephalosporanic acid (7-ADCA) was investigated to obtain 2-(3-amino-2-oxo-1-azetidinyl)-3-methyl-2-butenoic acid derivative (3a), a useful intermediate in a synthesis of monobactam compounds. The desulfurization of 7-ADCA gave a monocyclic β-lactam 3a and an unexpected 5-oxazolone derivative 5a. Compound 5a would be formed by the lactonization of alanyldehydrovaline derivative 4 derived from the hydrogenolytic cleavage of N-C4 bond of β-lactam ring in 7-ADCA. Similarly the desulfurization of cephalexin with Raney nickel gave the monocyclic β-lactam 3b and the 5-oxazolone derivative 5b. Compound 3a on treatment by the reported procedure gave 3-amino-2-azetidinone-1-sulfonic acid (7). Monobactam compounds 8 were obtained by acylation or arylation of 7. None of compounds 8a-e showed in vitro antibacterial activity against gram-positive and -negative bacteria.
This investigation was carried out to prepare each of the optical isomers of selenomethionine to be used for some biochemical studies. In order to obtain the D- or L-isomer from commercial DL-selenomethionine, it was incubated with immobilized amino acid oxidase at 37°C, and the incubation mixture was passed through Dowex 50W-X2 column. Preparation of the D-isomer from the L-isomer was performed by racemization of the L-isomer with amino acid racemase, followed by degradative removal of the L-isomer from the formed racemate with L-amino acid oxidase. These results also showed that amino acid oxidases and amino acid racemase used in this experiment react with selenomethionine.
Adsorption of insulin was studied by using glass ampule, silicone-coated glass ampule and polyvinylchloride tube. Insulin was well adsorbed onto silicone-coated glass ampule and polyvinylchloride tube. It is suggested that the preferential adsorption of insulin on silicone-coated glass ampule and polyvinylchloride tube is probably the result of hydrophobic interaction between hydrophobic moieties of insulin molecule and hydrophobic portion of these containers. Phenomenon of this adsorption is assumed to be competitive interaction between hydrophobic moieties of insulin molecule and some substances on hydrophobic portion of containers. I have tried to prevent the adsorption of insulin on containers by adding various kinds of surface-active substance which have hydrophobic group in molecule and rich solubility in water. In conclusion, adsorption of insulin can be remarkably decreased by the slight addition of surface-active substance.