Cation-nutrient cotransport is ubiquitous in nature. For cotransport, coupling between H⁺ and substrate is common in microbial cells, and that between Na⁺ and substrate is common in animal cells. We have reported that the melibiose transport system of Escherichia coli could utilize Na⁺ as a coupling cation. This is the first example of Na⁺-substrate cotransport found in microbial cells. Versatility in the combination between cation and substrate was revealed. This system seems to be a suitable model system for the analysis of cation-substrate cotransport systems. Physiological, biochemical and genetical properties of this system are summarized.

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New saponins, named gypenosides XV (1), XVI (2), XVII (3), XVIII (4), XIX (5), XX (6) and XXI (7) were isolated from Gynostemma pentaphyllum MAKINO. On enzymatic hydrolysis, 1, 2, and 3 yielded 20-O-β-D-glucopyranoside of 20 (S)-protopanaxadiol (compound K) (8), and 4, 5, 6 and 7 afforded 20-O-β-D-glucopyranoside of dammar-24-ene-3β, 12β, 20 (S), 26-tetraol (9) as a prosapogenin. The configuration of the sugar linkages in each saponin was established on the basis of chemical and spectroscopic evidence.

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Ethyl N-acetoacetylglycinate (1a), which was easily prepared from ethyl glycinate and diketene, was treated with hydrogen azide in concentrated sulfuric acid (Schmidt reaction) to give ethyl N-(N-acetylglycyl) glycinate (2a). Similarly, N-(α-alkylated acetoacetyl) glycinates 1b-f were transformed into the corresponding N-acetyldipeptides 2b-f by the Schmidt reaction. Treatment of optically active N-acetoacetyl-l-3-phenylalanine (3a) and N-acetoacetyl-l-leucine (3b) with hydrogen azide afforded N-(N-acetylglycyl)-3-phenylalanine (4a) and N-(N-acetylglycyl)-leucine (4b), respectively.

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Quantitative analysis of the tertiary alkaloids in various parts of Uncaria rhynchophylla MIQ. was made by use of high performance liquid chromatography (HPLC). The best result was obtained in the following conditions : column ; Radial Pak C₈ and mobile phase ; CH₃CN-0.05M AcONH₄ buffer (pH 4.0) [90 : 10]. The result revealed that the constitution of the alkaloids varied markedly depending on the botanical parts examined. While oxindole alkaloids (1, 2, 3 and 6) occupy ca. 97% of total alkaloids in hook, small stem and leaf, respectively, content of indole alkaloids (mainly 8 and 10) is almost exclusive (ca. 96%) in the bark of underground part. In the bark of aerial part both oxindole and indole alkaloids were found to be contained in nearly equal amounts. The alkaloidal content is very low in the wood (aerial or underground part) but the content ratios of rare alkaloids (4 and 7) to the total alkaloids are higher than the other parts.

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N-(2-Acyloxyethyl)-N, N-dimethyl-N-(1, 3-dioxolan-2-and 4-ylmethyl) ammonium compounds were synthesized and tested for anticholinergic activity. It was found that among these compounds the N-(2-acyloxyethyl)-N-(1, 3-dioxolan-2-ylmethyl) ammonium derivatives exhibited more potent activities than the N-(2-acyloxyethyl)-N-(1, 3-dioxolan-4-ylmethyl) ammonium and N-(3-acyloxypropyl)-N-(1, 3-dioxolan-4-ylmethyl) ammonium ones.

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16β-Ethyl-17β-hydroxyestr-4-en-3-one (oxendolone) (1), a new antiandrogen, was synthesized starting from dehydroepiandrosterone (2). 3β-Acetoxy-16β-ethylandrost-5-en-17β-ol (3), prepared from 2 by stereospecific introduction of 16β-ethyl substituent, was converted into 3β, 17β-diacetoxy-5α-chloro-16β-ethyl-androstan-6β-ol (5) by acetylation and then chlorohydrination. Treatment of 5 with lead tetraacetate gave 3β, 17β-diacetoxy-5α-chloro-16β-ethyl-6β, 19-oxidoandrostane (6) in 96% yield. 6 was transformed into 17β-acetoxy-16β-ethyl-6β, 19-oxidoandrost-4-en-3-one (8) by two steps. Reductive cleavage of an oxido bond of 8 with zinc followed by oxidation with pyridinium chlorochromate yielded 17β-acetoxy-16β-ethylandrost-4-ene-3, 19-dione (10) in 75% yield. Treatment of 10 with sodium hydroxide followed by acid hydrolysis gave 1 in good yield.

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On the basis of the mechanism of action of new antiandrogens, 16β-alkyltestosterones (1) and 16β-alkyl-19-nortestosterones (2), we designed and synthesized a series of 17-deoxyandrost-4-en-3-ones (12-14, 16, and 19) having substituent (s) at C-1, C-6, and C-7 positions and 17-deoxy-16β-alkylestr-4-en-3-ones (6) together with 17-deoxytestosterone (7) and 17-deoxy-19-nortestosterone (6 : R=H). The antiandrogenic activity was determined using immature orchiectomized rats treated with testosterone propionate. These compounds except 6 were found to show considerable antiandrogenic activity by subcutaneous or oral administration. The biological result means that 17β-hydroxyl group on the steroids was not indispensable for the manifestation of antiandrogenic activity. A new formylation reaction using orthoformate-boron trifluoride etherate instead of Vilsmeier reagent was described for the preparation of 6-formyltestosterone derivatives (9 and 22)

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In order to obtain specific antisera used for enzyme immunoassay of dexamethasone, dexamethasone-21-hemisuccinate (I), dexamethasone-6-carboxymethyl thioether (II) and dexamethasone-3-(O-carboxymethyl) oxime (III) were synthesized. Each compound was coupled with bovine serum albumin (BSA) by mixed anhydride method or carbodiimide method, and the complex was immunized in rabbit. As a labelled compound, alkaline phosphatase was conjugated with I, II and III using water-soluble carbodiimide. Bound and free dexamethasones were separated by the double antibody method. The specificity of each antiserum was assessed by determining cross-reactivity of other corticoids by means of enzyme immunoassay. Anti-II-BSA and anti-III-BSA antisera had higher specificity than that of anti-I-BSA antisera. Anti-II-BSA and anti-III-BSA antisera were purified by the method of affinity chromatography packed with betamethasone-3-(O-carboxymethyl) oxime-, II-, and III-Sepharose 4B, respectively. Percent cross-reactivities against betamethasone, a C-16 epimer of dexamethasone, of purified anti-II-BSA and anti-III-BSA antisera decreased remarkably. Using these purified antisera, it was possible to determine the amount of 0.2-20ng per assay tube of dexamethasone, in the presence of 100-fold betamethasone.

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The effect of water vapor on physicochemical stabilities of ground mixtures of crystalline medicinals with microcrystalline cellulose (M.C.C.) was examined under various conditions of relative humidity (R.H.). Physicochemical stabilities of ground mixtures were measured by X-ray diffraction method and thermal analysis. In the case of the 10% diazepam and 90% M.C.C. ground mixture, the presence of diazepam crystal was observed at 30°C and 84% R.H., while nicotinamide crystals were not observed for the 10% nicotinamide and 90% M.C.C. ground mixture at 30°C and 100% R.H. It was estimated that hydrogen bonds in the cellulose were broken on moisture adsorption and that medicinal molecules or microassemblies of the molecules dispersed within the cellulose obtained the ability to move. And then diazepan molecules or microassemblies of the molecules were crystallized because of its poor solubility and nicotinamide, very soluble medicinal, was hydrated with adsorbed water or adsorbed water and the cellulose.

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Pharmacokinetic parameters estimated using a program SIMPLEX based on a direct search method with a microcomputer were compared with those using the well-established nonlinear regression program NONLIN based on the Hartley's modification of the Gauss-Newton method with a large computer. Comparison of parameters calculated using these programs gave excellent agreement. Average computational time for the SIMPLEX was 7.1 min for 12 sets of data analyzed in this study and the computational time was reduced by 50% with a basic compiler. Parameters of the SIMPLEX in this study were compared to those of simplex method incorporated into MULTI program by Yamaoka et al. for microcomputer. Further, it was found that the combined use of SIMPLEX and NONLIN compensates several disadvantages of NONLIN. From the above results, it was concluded that SIMPLEX performed with a microcomputer can be replaced by NONLIN.

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The influences of fasting on elimination of sulfonylurea (SU) compounds from plasma were investigated in rabbits after intravenous administration. When SU compounds were intravenously given under fasted conditions, their elimination from plasma decreased more significantly than that under feeding conditions. A marked effect was found in chlorpropamide among SU compounds studied. A possible reason of the decrease of elimination rate constants of SU compounds in fasted rabbits was studied using chlorpropamide. The decreased renal tubular secretion and the increased renal tubular reabsorption of chlorpropamide observed under fasted conditions were considered to be possible reasons of the decreased elimination of SU compounds from plasma.

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Critical micelle concentrations (cmc) of the mixed solutions of glycyrrhizin and sodium cholate were determined by the measurements of light absorption of aqueous iodine solution and solubility of yellow-OB as well as the measurements of surface tension. Critical micelle concentrations of the mixed solutions determined by these methods were relatively in good agreement with each other. The cmc increased with increasing the mol fraction of sodium cholate and pH. It was found that the cmc of mixed solutions and the composition of mixed micelles were in conformity with the theory of ideal mixing. The facts suggest that glycyrrhizin contributed effectively to the formation of mixed micelle. The mol fraction of glycyrrhizin in mixed micelle increased with decreasing pH.

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The roots of Angelica ursina MAXIM. (Umbelliferae) afforded seven known coumarins, glabra-lactone (1), osthol (2), xanthotoxin (4), bergapten (17), 7-methoxy-8-senecioylcoumarin (18), coumurrayin (19) and glabra-lactone hydrate (20) as well as a mixture of angelols (21). Further it became clear that 21 consisted of the group I-IV of angelols on the basis of ¹H nuclear magnetic resonance spectral analysis and thin layer chromatography, though they are not yet investigated exactly. On the other hand the seeds of this plant afforded six known coumarins, imperatorin (3), umbelliprenin (8), heraclenin (22), heraclenol (23), tert-O-methylheraclenol (24) and 8-geranoxypsoralen (25).

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Reaction of diene (1) with dienophiles (2), (3), and (4) were carried out in order to examine the behavior of 1 as enophile. These results showed that 1 was prone to give Michael adduct rather than Diels-Alder adducts as dienophile became more reactive.

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A spectrophotometric analytical method for the determination of aldioxa (AL), an anti-peptic ulcer agent, in pharmaceutical preparations has been established. Hydrolysis of AL gives allantoic acid (AA) which is transformed into glyoxylic acid (GA) in the presence of hydrochloric acid. GA reacts with phenylhydrazine to form Shiff base, glyoxylic acid phenylhydrazone (GAP), which has an absorption maximum at 335 nm. The correlation coefficient between the absorbance and amount of AL was 0.999, and the coefficient of variation 0.33-0.63%. This method is considered to be useful for the routine analysis of AL in pharmaceutical preparations.

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Catalytic hydrogenation of acridone alkaloids over platinum catalyst under acidic conditions was examined. The A-and/or C-ring in acridones having only O-substituents were hydrogenated together with hydrogenolytic elimination of O-substituents. On the other hand, the C-ring in pyranoacridones was found to resist the hydrogenation even in acidic solution.

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