Absorption properties of an ion pair complex, quinine and bromthymol blue (BTB), were investigated by the rat small intestine. Although the disappearance of quinine from the in situ recirculated solution was enhanced in the presence of BTB and the converse was not applied for the anionic component, the enhancement of uptake by the everted intestine was observed by both components. By rinsing the everted intestine at the end of an incubation period, no effect of quinine on the tissue accumulation of BTB was found. Effect of counter ions on the binding to mucosal homogenates, brush borders, and bovine serum albumin (BSA) was hardly observed at all. Pretreatment of the intestine with pH 6.5 phosphate buffer for 10 min almost completely diminished the enhancing effect of BTB on the disappearance of quinine from the in situ recirculated solution. However, 15 min was enough after the pretreatment to regain such an enhancing effect of the anionic component. It is suggested that the mucosal surface of the small intestine plays an important role in the absorptive process of an ion pair complex.

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3-Alkylamino-(cis-1a-c) and trans-1a-c), 7-hydroxy-3-isopropylamino-(cis-1d and trans-1d), 7, 8-dihydroxy-3-isopropylamino-(cis-1e and trans-1e) and 6, 7-dihydroxy-3-isopropylamino-4-chromanol (cis-1f) were synthesized. By the use of lithium cyanoborohydride (LiBH₃CN), the reductive N-alkylation of 3-amino-4-chromanones with acetone proceeded smoothly to produce 3-isopropylamino-4-chromanones (12e and 12f) in good yields. Stereoselective hydrogenation of 4-chromanones in a basic or an acidic medium to give trans- or cis-aminoalcohols was discussed on the basis of the thermodynamic stability of the end products. Among the compounds synthesized, 7, 8-dihydroxy derivatives showed a strong β₂-stimulating activity, whereas the 6, 7-dihydroxy congener was devoid of the activity. The results suggest an important role of the spatial arrangement of functional groups in these catecholamine molecules with regard to their pharmacological properties.

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Experiments were made to clarify the relationship between surface view of powder particles of sulfonamide and their initial dissolution behavior, and the following results were obtained. 1) A particle surface appearance, in each particle size grade sieved from commercial sulfisomezole and sulfamethizole, and recrystallized sulfanilamide, was observed by scanning electron microscope and very fine particles adhering on the particle were found irrespective of particle size. Very fine adhering particles were scarcely found on the recrystallized particles. To remove the very fine adhering particles, these samples were treated with distilled water, 0.2% sodium lauryl sulfate solution, saturated solution of sulfonamide, or 0.2% sodium lauryl sulfate solution saturated with sulfonamide. Surface appearance of these treated samples revealed no adhering particle on the particles except for those treated with saturated solution of sulfonamide. Agglomerated ball-milled samples were composed of very fine particles of diameter ranging from 0.1 to 1 μm. 2) Examination of initial dissolution rates revealed that an increase of instantly dissolving parts with decrease in particle size was due to the very fine particles adhering on the particle, but, in spite of no adhering particles on the particle, the instantly dissolving parts also increased with decrease in particle size. This result supports the observation that surface free energy of powder particles may play an important part in the initial dissolution with decrease in particle size. The instantly dissolving parts of ball-milled sample increased greatly for each sulfonamide and it was around 25% of saturation.

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A new polyoxypregnane derivative, tomentomin (12β-O-cinnamoyl-20α-O-nicotinoyltomentogenin), was isolated from the leaf of Marsdenia tomentosa. Tomentomin is the first tomentogenin derivative with nicotinic acid in ester-linking to be isolated from Asclepiadaceae plants.

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The interaction of N-methyl-2-pyrrolidone (NMP) with aminobenzoic acids was studied, observing the effect on the solubility of aminobenzoic acids in ether in comparison with that of N-ethyl-2-pyrrolidone (NEP). p-Aminobenzoic acid (PABA) and p-aminosalycilic acid (PAS) formed slightly soluble complexes in ether with NMP, while the other aminobenzoic acids formed soluble complexes in ether. From the solubility data, the stoichiometrical ratio and the stability constant K of the formation of complex were calculated. K value was strongly affected by the orientation of the substituent group and the existence of the hydroxyl group in aminobenzoic acid, as the decreasing order for NMP-aminobenzoic acids complexes was as follows : PABA>anthranilic acid (ANA)>m-aminobenzoic acid. K value for NEP complexes decreased in comparison with that for NMP complexes. This may be due to the steric hindrance of ethyl group in NEP. On the other hand, the complex formation in solid phase was recognized in NMP-PABA, NMP-PAS, and NMP-ANA systems by powder X-ray diffractometry and IR absorption spectroscopy. The dissolution rate of these solid complexes was studied by stationary disk method, and it was found that the complexes dissolved fast compared with the respective original compounds. These results suggested that the complex formation with NMP may enhance the bioavailability of drugs.

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Three isomers of meso-tetrapyridylporphins, i. e. tetra (2-pyridyl)-(2), (3-pyridyl)-(3), and (4-pyridyl)-(4), porphin have been synthesized. They were soluble in acetic acid, chloroform and acidic aqueous solvents. Solubilities in chloroform, dimethylformamide and pyridine were in the order 3>2>4. Comparison of the visible spectra indicated that the intensities of the bands due to 0-0 transitions decreased (3>4>2) with an increase of the electron-withdrawing character of the pyridyl substituent. The copper (II) and zinc (II) complexes of 2 and 3 have been prepared. Infrared and nuclear magnetic resonance spectra and their assignments of the porphins and/or the metal complexes were described.

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As part of a study on the structure-activity relationships of the partial agonist activity of phenylazabicycloalkane analgetics, the title compound (I), a five membered alicyclic analog of the known analgetic agent (II), has been synthesized. The aminoketone (V) was converted to I via the 8-oxo derivative (VII) by the usual method. Alternatively, intramolecular Michael reaction of the amino cyclopentenone derivative generated in situ by hydrolysis of the urethane (X) gave the 6-oxo derivative (XII) convertible also to I. Finally and most conveniently, the keto enamines (XVI and XVII), obtained by mercuric acetate oxidation of XIV and XV, were cyclized to XVIII and XII by heating them with aqueous acetic acid, respectively. I was found to be analgetically inactive but exhibited narcotic antagonsit activity comparable to pentazocine. Certain structural correlations between I and other phenylazabicycloalkane analgetics are discussed.

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Effects of the gastric juice inhibitory substance (GIS) from the culture filtrate of Streptomyces bottropensis F4708 to several kinds of experimental gastric ulcers and gastric juice secretion in rats were studied. GIS inhibited ulceration in pylorus-ligated rats, and also markedly reduced gastric juice secretion. Moreover, it reduced aspirin-induced lesions in pylorus-ligated rats by lowering the gastric acidity. It showed a little effect on the healing of acetic acid-induced gastric ulcer. However, it isn't effective against stress-induced gastric lesions or histamine-induced ulceration. GIS reduced gastric acid secretion in vagotomized rats, and also, though with a little lowered activity, reduced gastric juice secretion in reserpine-treated rats. The protein part of GIS was proved to be important in the action of GIS but its dark brown pigment part alone could make effect. GIS lowered the body temperatures of rats.

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A simple, rapid, and accurate high-speed liquid chromatographic method was established for the determination of ecdysterone (I) and inokosterone (II) in Achyranthis radix. I and II, extracted from Achyranthis radix, were directly injected onto column and separated in approximately 15 min using a 2 m Permaphase ETH column with a mobile phase of 10% ethanol in n-hexane at 50°. A working relative standard deviation was less than 2%. The extraction methods were also investigated and it was concluded that the Soxhlet extraction with methanol was the most effective. Moreover, II was separated into two epimeric isomers on a Permaphase octadecyl silane column with a mobile phase of methanol in water.

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Molecular orbital studies were carried out on α-chymotrypsin, papain, and thiolsubtilisin by using the complete neglect of differential overlap/2 method. By comparison between α-chymotrypsin and papain, the following results were obtained : (1) The proton transfer barrier from Cys-25 (neutral) to His-57 (neutral) is lower than that from Ser-195 (neutral) to His-57 (anion) in the"charge relay system"of α-chymotrypsin. (2) The active site of papain does not have the"charge relay system"and asparagine facilitates the proton transfer from cysteine to histidine. The results for thiolsubtilisin were as follows : (1) The hydrogen bond system structure in the active site is aspartate (neutral)-histidine (neutral)-cysteine (anion), and the"charge relay system"is broken by cysteine in place of serine. (2) Even though the effect of solvent is present, cysteine anion is stable. A"charge relay system"composed of aspartate, histidine, and water dimer was proposed from the calculations by using water dimer in place of serine.

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A new fluorometric method for the sensitive assay of human serum monoamine oxidase is presented. This is based on the determination of benzaldehyde produced from the substrate benzylamine under the optimal enzyme reaction conditions by means of the previously established fluorometric method for selective determination of aromatic aldehydes with 1, 2-diaminonaphthalene sulfate. This method gives reliable results and is readily performed with a minimum amount of serum.

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Phenolic oxidation of 1, 2, 3, 4-tetrahydro-6, 7-dihydroxy-1-(4-hydroxy-3-methoxyphenethyl)-2-methylisoquinoline (14) with ferric chloride gave the homoproaporphine (15), isolated as the corresponding diacetate (16), which would be a key intermediate to kesselringine (6) from chemical and biogenetic points of view.

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Several structure-activity data which had been analysed using molar attraction constant, partition coefficient, connectivity index, and molar refraction as a parameter for drug structure were reexamined by the use of van der Waals volume (V_W). These data included actibacterial activity of penicillins, tadpole narcosis with miscellaneous compounds, inhibition of neuraminidase by dihydroisoquinolines, fungus toxicity with miscellaneous molecules, inhibition of xanthine oxidase by phenylguanines, and tuberculostatic activity of isoniazid derivatives. In all the cases, very significant correlations were found by regression analysis. These findings supported the generality of the use of V_W to analyse and predict biological activity relating to molecular structure.

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The biological active substances in the venom of hornet (Vespa xanthoptera) on the rat uterus, the rat arterial blood pressure, the guinea pig ileum and the rabbit erythrocytes were investigated. A new type of bradykinin analogous peptide, vespakinin-X, was identified as hornet-kinin. The amino acid sequence of vespakinin-X has been found to be Ala-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-Ile-Val. In addition to the presence of vespakinin-X, histamine, acetyl choline-like substance and large amounts of serotonin were demonstrated in the venom.

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Isolation and characterization of the conjugated metabolites excreted in rat bile following the oral administration of a large dose of estriol has been undertaken. The principal conjugates (I-XI) were separated by chromatography on Amberlite XAD-2 resin, followed by gel filtration on Sephadex LH-20 and partition chromatography on silica gel. The structures of these metabolites were deduced from the physico-chemical data and definitely characterized by leading to the known derivatives and their comparison with the synthetic specimens. The physiological significance of biotransformation hereby observed has also been discussed.

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Previously 2'-O-(o-nitrobenzyl) uridine was synthesized via 2', 3'-O-(stannylene) uridine and used in the synthesis of UpA and UpU. 2'-O-(o-Nitrobenzyl) derivatives of cytidine and adenosine were synthesized with o-nitrobenzyl bromide in the presence of sodium hydride. 3'-O-(o-Nitrobenzyl) cytidine was also isolated. Using these 2'-protected nucleosides, partially protected trinucleoside diphosphates, CpA (o-nitrobenzyl)-pA and CpCpA (o-nitrobenzyl) were synthesized using a diester method or a triester method. These oligomers are candidates as suitable substrates of ribonucleic acid (RNA) ligase. Removal of the o-nitrobenzyl group was effected by irradiation with ultraviolet spectrum (UV) light (wavelength longer than 280 nm) and the completely deblocked oligonucleotides were characterized by enzymatic hydrolysis.

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The carbon magnetic resonance spectra of trans-(I) and cis-N-methylquinolizidinium ion (II) were examined in relation to the stereochemistry of these compounds. Ring inversion of the cis-N-methylquinolizidinium ion was observed in variable temperature experiments and results afforded ΔGc^≠=13.7 kcal/mole. The observed carbon chemical shift difference between I and II was compared with that estimated empirically, and shown to be a measure of the stereochemical difference between the trans-and cis-forms of the quinolizidine nucleus.

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Reactions of pyridine (I, IV, X, XIII) or condensed pyridine (VII, XVI, XVIII) N-oxides with formamide were described. Although pyrimidinyl cyclization of active methyl group was unsuccessful, introduction of carbamoyl group at pyridine ring carbon adjacent to nitrogen atom was successful, i. e., 6-methylpyridine-2-(II), 4-methylpyridine-2-(V), 4-methylquinoline-2-(VIII), 5-methylpyridine-2-(XI), pyridine-2-(XIV), quinoline-2-(XVII), and isoquinoline-1-(XIX) carboxyamides were obtained.

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Paniculatan, the mucous polysaccharide isolated from the inner barks of Hydrangea paniculata SIEB., was found to be composed of L-rhamnose : D-galactose : D-galacturonic acid : D-glucuronic acid : 4-O-methyl-D-glucuronic acid in the approximate molar ratio of 4 : 4 : 3 : 2 : 5. The mucilage has been subjected to the reduction of carboxyl groups and to controlled Smith degradation. As the results of methylation analysis of these products and the original polysaccharide, possible structures of the backbone chain were proposed. The chain is composed of 1→2 linked L-rhamnopyranose residues having branches at position 4 and 1→4 linked D-galactopyranosyluronic acid residues having branches at position 3 in the approximate molar ratio of 2 : 1.

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Ozonolysis of phenolic dehydroabietic acid derivatives with an isopropyl group at 13-position was investigated and the direction of cleavage of the aromatic ring by means of ozonolysis was found to be affected by the substitution pattern of hydroxyl group in the aromatic ring. Ozonolysis of the 12-hydroxy ester (12) afforded the pentanorlabdane type compounds, (13), (14), and (15), while ozonolysis of the 14-hydroxy ester (17) and (18) gave the drimane type products, (19) and (20).

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A new triterpene acid, named barbinervic acid (I) has been isolated from the leaves of Clethra barbinervis SIEB. et ZUCC. and barbinervic acid was elucidated as 3α, 19α-24-trihydroxyurs-12-en-28-oic acid by chemical and spectral evidences. Besides, rotundic acid was also isolated.

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The relative stability of equatorial vs. axial for methyl groups on nitrogens in diprotonated N, N'-dimethylpiperazine was determined from the total energy differences of six possible conformers using the Unrestricted Open Shell SCF-MO INDO Method, and the result was in accord with the observed value of our previous paper obtained from the curve of dielectrometric titration. An equatorial methyl group bonded to the chair form piperazine ring was more stable than that of an axial position by an amount of 1.38 kcal/mol from computer analysis, which was fairly coincident with the observed value of 1.6 kcal/mol obtained from the dielectrometric titration.

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Dialkyl acylphosphonate worked as an acylating agent on 2-methylthiazolium and thiazolinium salts in the presence of base, to give 2-acylidenethiazoline and thiazolidine derivatives, respectively. Dialkyl [1-aryl (alkyl)-1-dialkylphosphatomethyl] phosphonate was also isolated as a by-product in the same reaction. Dialkyl acylphosphonate afforded 2-acylidenethiazolines in better yield compared with acyl chlorides and showed on apparent affinity for carbanions. Application of diethyl benzoylphosphonate to 1, 2, 3-trimethylbenzimidazolium iodide, however, formed a dimeric salt, 1, 1', 3, 3'-tetramethyl-2, 2'-(2-phenyltrimethylene) di (benzimidazolium) diiodide in addition to 2-(1, 3-dimethylbenzimidazolin-2-ylidene) acetophenone. On the basis of the reactivity difference between the 2-methylthiazolium and 2-methylimidazolium salts and the kinetic experiments, the mechanism of the acylating reaction was proposed.

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Five polymorphs (A-, B-, C-, D- and E-form), four solvates (monohydrate, a hydrate contained 3/4 molecule of water, methanol monosolvate and a solvate contained 4 molecules of methanol and 1 molecule of water) and an amorphous form of calcium DL-pantothenate were isolated. These crystal forms were characterized using thermal analysis, X-ray powder diffraction and infrared spectroscopy. In order to examine the resolution of calcium DL-pantothenate by preferential crystallization, the racemic structures of these crystal forms were investigated by comparing these physical properties with those of crystal forms of calcium D (+)-pantothenate. As the results, C-form and the solvate contained 4 molecules of methanol and 1 molecule of water were found to be the racemic mixtures and then the optical resolutions of the two kinds of crystals were carried out.

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Hyaluronidase, N-acetylglucosaminidase and β-glucuronidase of rat carrageenin granuloma were isolated and partially characterized, and changes in these enzyme activities during development of granuloma were also examined in order to clarify the role in metabolism of mucopolysaccharides of the granulomatous tissue. The exo-polysaccharidases, N-acetylglucosaminidase and β-glucuronidase, were present in both the granuloma and the pouch fluid, but hyaluronidase was dected only in the pouch fluid. After the gel filtration of pouch fluid on Sephadex G-200, hyaluronidase was separated completely from the two exo-polysaccharidases, and its enzymatic properties were examined. Optimum pH for the activities of hyaluronidase and N-acetylglucosaminidase was different from that of β-glucuronidase. The hyaluronidase fraction obtained was capable of degrading macromolecular hyaluronate and this fraction also depolymerized chondroitin 4-sulfate and 6-sulfate, but not dermatan sulfate. Appearance of these enzymes in the pouch fluid was periodically independent of one another ; maximum hyaluronidase activity was shown at 8 days after carrageenin injection and at initial experimental stage, higher N-acetylglucosaminidase was detected. On the other hand, β-glucuronidase was almost constant during the experimental period. The degradation of hyaluronic acid and the granuloma slices by hyaluronidase was not increased by the addition of N-acetylglucosaminidase and β-glucuronidase.

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Pharmacological properties of preparations from Panacis Japonici Rhizoma were studied by the screening methods consisting of 5 tests. CNS-depressant, tranquillizing, cholinergic, anticholinergic, histamine-like, antihistamine-like, antinicotinic, blood pressure elevating and lowering, and antiinflammatory activities were estimated. Chikusetsusaponin III whose aglycone is 20S-protopanaxadiol is especially remarkable as it has tranquillizing, anticholinergic, antihistamine-like, antinicotinic, and blood pressure elevating and lowering activities. Cholinergic, histamine-like and blood pressure elevating activities were found in the fraction which did not contain saponins. Antiinflammatory activity was estimated to chikesetsusaponin V.

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A new rotenoid, clitoriacetal (I), has been isolated from the crude drug named"Nontai-yak, "which was identified as the root of Clitoria macrophylla WALL. CAT. (syn. C. hanceana HEMSL., Leguminosae) by the comparison with the authentic specimen, together with a known rotenoid, stemonacetal (II). The structure of clitoriacetal was elucidated to be I by chemical and spectral analysis.

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The effects of insulin on the transmucosal fluid movement and the intestinal absorption of sulfisoxazole and metoclopramide in alloxan diabetic rats were studied with perfusion solution adjusted to isotonicity with sodium chloride using the in situ recirculating perfusion method. Insulin was intravenously administered to diabetic rats in a dose of 3 unit/kg of body weight and the perfusions were started at one and half an hour after the hormone administration. When insulin was injected to the diabetics to decrease the high blood glucose, the transmucosal fluid inflow and the drug absorption were decreased along the corresponding regression line representing the relations between the blood glucose and the transmucosal fluid movement, and the drug absorption. The fluid inflow and the drug absorption from the entire small intestine and per unit dry weight of the intestine were always significantly less in the insulin received group than in the diabetic group. Moreover, the effect of insulin on an actively transported sodium absorption was also studied to compare with that of the drugs. A similar observation was obtained in this case. A possible mechanism of these decreased absorptions by insulin was discussed.

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Dissolution of 3-methoxy-17β-methyl-18-norestra-1, 3, 5 (10), 13-tetraene into 77.3% sulfuric acid gave the chromophore χ-372 (I) which changed gradually to χ-465 (II). This change was faster and its acceleration with oxidant was greater in the systems of lower acid strength. In 97.2% sulfuric acid, 3-methoxyestra-1, 3, 5 (10), 9 (11)-tetraen-17-one and 3-methoxyestra-1, 3, 5 (10), 8, 14-pentaen-17-one showed maximum absorptions at 363 and 467 nm, respectively, and were then recovered almost quantitatively from the solution. Thus, the conjugate base of I was assumed to give II through an oxidative process. 13ξ, 14ξ-Epoxy-3-methoxy-17β-methyl-18-norestra-1, 3, 5 (10)-triene (III) immediately showed a stable maximum absorption at 465 nm in 97.2% sulfuric acid, from which the estrapentaene (IV) was then isolated. Compared with the chemical shifts of I, NMR spectra of III as well as IV in sulfuric acid suggested II to be the carbocation. The same experiments were also made on related compounds and corresponding results were obtained. Consequently, it is proposed, for the mechanism of the Kober reaction in its first stage, that the conjugate base of the initially formed carbocation χ-372 (I) is oxidized by sulfuric acid into the chromophoric cation χ-465 (II).

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The title new reducing disaccharide (12) was synthesized starting from 1, 6-anhydro-β-lactose. Selective benzoylation of 1, 6-anhydro-4', 6'-O-benzylidene-β-lactose with 4 molar equivalents of benzoyl chloride in pyridine afforded the corresponding 2, 3, 3'-tri-O-benzoate (3) in 41% yield. Sulfonylation of 3 gave 2'-O-mesylate (4) or 2'-O-tosylate (6). Treatment of 4 or 6 with 1.1 molar equivalents of sodium methoxide in boiling MeOH yielded 1, 6-anhydro-4-O-(2, 3-anhydro-4, 6-O-benzylidene-β-D-talopyranosyl)-β-D-glucopyranose (7) in 50 or 66% yield. Further crop of 7 was isolated from the filtrate of 7 as the corresponding diacetate. Heating of a mixture of 7 with excess aq. KOH at 100° for 3 hr cleaved the epoxide ring of 7 trans-diaxially and, after acetylation, 2, 3-di-O-acetyl-1, 6-anhydro-4-O-(2, 3-di-O-acetyl-4, 6-O-benzylidene-β-D-idopyranosyl)-β-D-glucopyranose (9) was isolated in 84% yield. Debenzylidenation of 9 followed by acetylation, and subsequent opening of the 1, 6-anhydro-β-ring with titanium tetrachloride in CHCl₃, then treatment with mercuric acetate in glacial AcOH, afforded 1, 2, 3-tri-O-acetyl-4-O-(2, 3, 4, 6-tetra-O-acetyl-β-D-idopyranosyl)-β-D-glucopyranose (11) in 43% yield. Deacetylation of 11 afforded the title compound (12) as a hygroscopic, amorphous powder which gave the crystalline tosylhydrazone.

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The ternary complex [Cu (AdeH) (Ade) (phen)₂OH]₂·2H₂O has been prepared and compared with the binary complexes. The mixed ligand complex was characterized from elementary analysis and infrared spectra. From the shift of the aromatic carbonaliphatic nitrogen stretching in infrared spectra, it is expected that the amino group of adenine ligand would not coordinate to copper (II), and consequently, it is likely that N9 of adenine ligand coordinates to copper (II) in the mixed ligand complex. The triplet state electron spin resonance spectra of the mixed ligand complex were recorded and the results interpreted in terms of a dipole-dipole interaction between pairs of copper (II) ions in a dimeric complex.

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Aroyl esters of 2-N, N-dialkylamino-1-benzocycloalkanols (6, 7), which may be considered to be semi-rigid cyclic analogs of procaine, were prepared to study the influence of the stereochemical relationship between the aroyloxy and the amino group on local anesthetic activity. The cis-compounds (6a-1, 6c-1) were more active than the corresponding trans-isomers (6b-1, 6d-1). Similarly, the optical isomers of cis-2-N, N-dimethylamino-1-benzoyloxy-1, 2, 3, 4-tetrahydronaphthalene (6c-1) differed in their activity with the l-isomer being more active. The reaction of 2-bromo-1-tetralol (9) with dimethylamine was also discussed.

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Micellar interactions of tetracycline, oxytetracycline, chlortetracycline and minocycline were examined in aqueous solutions of polyoxyethylene lauryl ether (PLE), sodium lauryl sulfate (SLS) and dodecyltrimethylammonium chloride (DTAC) at various pHs (2.1-5.6) by dynamic dialysis. The respective partition coefficients of ionized and zwitterionic species were calculated. The ionized species of the antibiotics except for minocycline were more solubilized than zwitterionic ones in PLE solution, in which the orientation of hydrophobic parts of the antibiotic and micelle structures plays a primary mechanism for their interaction. In ionic surfactant solutions, the electrostatic force was predominant at lower pH and the solubilization capability of the anionic surfactant was much higher than that of the cationic one for tetracycline over the pH range examined.

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Taking into account the possible effect of the polar group located in the side chain, the autoxidation of taurocholanic acid in neutralized aqueous solution was carried out with the ferrous ions-molecular oxygen system at 70° for 4 hours. The taurocholanates of the reaction mixture were collected on a column packed with XAD-2 resin, then saponified to the free bile acids, and finally esterified for convenience of purification to obtain the methylated products. Attack of the hypothetical ferrous dioxygen complex seemed to occur in the ring D as expected, since the structure of the product B was assumed to be methyl 15α-hydroxy-5β-cholan-24-oate. Thin-layer as well as gas-liquid chromatograms of the product A were in good agreement with those of authentic methyl lithocholate, indicating that the complex can also attack the ring A from α-side of the steroidal skeleton.

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Many kinds of drugs cause lysis of erythrocytes at higher concentrations. To clarify the mechanism of hemolysis, the effect of chlorpromazine and clemastine on the structure and arrangement of the membrane proteins and phospholipids was studied using circular dichroism (CD) and some hydrophobic probes, in addition to studies on the alterations in the components of the cells and using "pink ghosts"containing α-amylase. Initial experiments demonstrated that human erythrocytes were hemolyzed within several minutes at a higher drug concentration (1×10^-3 or 8×10^-4M), while a somewhat lower concentration (6 or 5×10^-4M) there was a lag phase for about 30 min and then resulted in severe hemolysis. Dramatic hemolysis occurred at a chlorpromazine concentration which approximately corresponds with the critical micellar concentration. The content of sulfhydryl groups in the cells and calcium in the membrane was not affected by the drug treatment. At above 2×10^-4M of both drugs, components I and II (spectrin) were released from the membrane. These drugs, however, had little or no effect on the CD spectra of the ghosts, suggesting that the drug-induced hemolysis is not due to the denaturation of the proteins. 1-Anilinonaphthalene 8-sulfonate (ANS)-ghost fluorescence and 2, 4, 6-trinitrobenzenesulfonate (TNBS) binding to aminophospholipids were extremely enhanced by the drug exposure. The enhancement of the ANS-ghost fluorescence and TNBS binding with drugs was almost paralleled with that of the hemolytic effect. These drugs thus disturb the arrangement of phospholipids and the hydrophobic interactions between lipids and proteins, and alter the membrane permeability, thereby appear to induce hemolysis.

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The direct effect of CCl₄ on leakage of cellular glutamic oxaloacetic and glutamic pyruvic transaminases of a line of hepatic tissue culture cell, HTC cell, into medium was quantitatively studied. Cellular levels of soluble isozymes of the both aminotransferases were considerably lowered by addition of CCl₄ to culture medium at a concentration of 10 mM followed by 48 and 96 hr of culture. Contrasting increase or less influenced decrease of enzyme activities in bathing fluid after treatment made the leaking indexes of the enzymes (cellular secretion of activities found in medium/cellular activities) twice or more as large as control depending on the concentrations of CCl₄ in medium and lengths of treatment. Simulating study on change of CCl₄ concentration in bathing fluid with time of culture showed a rapid and extensive fall of it upon the addition of CCl₄ with a later stable phase probably in equilibration with the agent in the gas phase within culture flask.

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About 45% inhibition of Ca²⁺-stimulated ATPase activity was observed with 24 mM F-, and only 50% inhibition of Mg²⁺-stimulated ATPase was shown with 24 mM F-. On the other hand, the Ca²⁺-stimulated ATPase activity in lung mitochondria of rats was significantly elevated by the administration of sodium fluoride (35 mg/kg i. p.), while the Mg²⁺-stimulated ATPase was not affected with the administration.

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Local anesthetic agents, benzocaine and butamben were compared for their permeabilities to silicone membrane and stabilities against hydrolytic degradations in 0.05N NaOH solutions. Butamben permeated through the membrane from the suspension to the same extent as benzocaine in spite of smaller solubility in water. Calculated stability of butamben in suspension was about 10 times greater than benzocaine due to smaller hydrolytic rate constant and smaller solubility. These properties of butamben may be favorable for the delivery system using a silicone membrane as a release-controlling barrier.

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The halogenation of 2-phenylethanol-1-¹⁴C and -1-¹³C was carried out with halogenphosphorus or phosphorus trihalide under various conditions. The resulting 2-phenylethyl halides showed isotopic scrambling of the ¹⁴C and ¹³C label from C-1 to C-2. The degree of rearrangement increased with the rise of reaction temperature. In a given temperature, the rearrangement in iodination was more than that found in bromination or chlorination.

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By use of stopped flow rapid scan spectrophotometric technics, it was demonstrated that the backward reaction from dihydroxylated anion (1 : 2 complex) derived from 1, 3, 5-trinitrobenzene with sodium hydroxide to monohydroxylated anion (1 : 1 complex) did not occur when the alkaline solution of 1, 3, 5-trinitrobenzene was neutralized or acidified with acids.

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A new synthetic route to 6, 7-benzomorphan has been developed. 2, 2-Dimethyl-7-methoxy-3, 4-dihydro-1 (2H)-naphthalenone (1) was cyanomethylated, followed by LiAlH₄ reduction and a Wagner-Meerwein rearrangement, to give aminoethyl compound 3. Treatment of 3 with bromine gave hydrobenz [e] indole 4, which was rearranged to 9-methylene-6, 7-benzomorphan 5. Hydrogenation of the methylene gave 5, 9α-dimethyl derivative 6, from which 5, 9α-dimethyl-2'-hydroxy-6, 7-benzomorphan (7) was obtained.

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Dissolution curves of colchicine in water, carbon tetrachloride, and benzene revealed that solvates are formed after initial dissolution of ansolvate with a resultant decrease in concentration in solution. An aqueous solubility-temperature profile exhibited a minimum in 25-45° range. Addition of trichloroethanol and chloroform to benzene resulted in increase in benzene/water partition coefficient of colchicine. Benzene/water and carbon tetrachloride/water partition coefficients were greater at higher temperature. Salt effects on benzene/water partition coefficient followed the Hofmeister series and the Setshenow relationship.

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In this paper, the particle size distribution of TiO₂ measured by a turbidimeter is compared with that of the micron photo sizer and, in succession, the validity of turbidimetry is discussed. After changes of the turbidity with time were measured, the particle size distribution was then evaluated indirectly from above data. Furthermore, the approximate formula of particle size distribution was calculated from an aspect of statistical analysis. In result, it was clearly observed that the particle size distribution calculated from the approximate formula was closely agreement with the ones measured by the turbidimeter and the micron photo sizer. It was, therefore, ascertained that the particle size distribution of powder was possible to be exactly measured by the method of turbidimeter.

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The nitrosation of 1-(2-chloroehtyl)-and 1-cyclohexyl-3-(3-pyridyl) methylureas with sodium nitrite and hydrochloric acid, gave a mixture consisting of the corresponding 1-and 3-nitroso derivatives. These isomers were successfully separated by fractional crystallization using diethyl ether. Their structures were confirmed by means of nuclear magnetic resonance spectroscopy and chemical reaction.

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Several 2'-phenyl-spiro [1, 3-dioxolane-2, 5'-indazoles] having alkyl or alkoxy side chains at 1'(III), 3'a (IV) and 3'(V) were prepared as analgesic agents. III and IV were derived to oxo-indazoles (VII, VIII), which were hydrogenated to give the corresponding hydroxy indazoles (IX, X). Some of these compounds showed slight analgesic activity.

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A treatment of N-(3-acetoxy-4-benzyloxyphenethyl)-4-benzyloxy-3-methoxyphenylpropionamide (17) with phosphoryl chloride gave 1-(3-acetoxy-4-benzyloxyphenethyl)-imino-6-benzyloxy-5-methoxyindane (21) instead of the normal product, 3, 4-dihydroisoquinoline (20). The structure of 21 was determined by chemical method and by an alternative synthesis of the indane derivative (25) derived from 21.

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This article reports histological study was made for crude drugs derived from Equisetum species. Six samples were examined and all were identified clearly : "S 378 muzei"( ?? ?? ), "KL 489 muxi"( ?? ?? ), and"188 muzei in Formosa"( ?? ??, ?? ?? ) were identified to be E. hiemale L. var. affine (ENGL.) A. A. EATON ; "S 400 (S 611) jiegucao"( ?? ?? ?? ) and"KL 490 bogucao"( ?? ?? ?? ) were E. ramosissimum DESF. subsp. debile (ROXB). HAUKE ;"30-40 cola de caballo"was E. giganteum L.

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2, 3-Dideoxy-2, 3-epithio-β-D-allofuranose (3c) and 2, 3-dideoxy-2, 3-epithio-α-D-mannofuranose (4c) were obtained, respectively, by the hydrolyses of methyl 2, 3-dideoxy-2, 3-epithio-α-D-allopyranoside (1a) and methyl 2, 3-dideoxy-2, 3-epithio-α-D-mannopyranoside (2a) with Amberlite CG-120 (H⁺) in H₂O. The structures of these reducing sugars were confirmed by nuclear magnetic resonance spectroscopy.

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N-Protected amino acyl-or peptidyl-resin was prepared in good yield without racemization, when about a half equivalent amount of 1, 5-diaza-bicyclo [4, 3, 0] nonene-5 (DBN) or 1, 8-diaza-bicyclo [5, 4, 0] undecene-7 (DBU) salt of N-protected amino acid or peptide was allowed to react with chloromethylated polystyrene-2%-divinylbenzene resin (chlorine content 0.66 millimole per gram) at 50°for 28 hours. The unchanged chloromethyl group was acetylated quantitatively by the reaction with large excess of DBN salt of acetic acid.

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An X-ray structure determination of 1-(3, 5, 5-trimethyl-1-pyrazolinyl) phthalazine, synthesized from 1-hydrazino phthalazine with mesityl oxide, was performed. The structure was solved by the heavy atom method and refined by least-squares procedures to an R factor of 0.048.

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