Several syntheses of insect pheromones are discussed so as to illustrate three different approaches for the synthesis of chiral compounds : i) derivation from natural products, ii) optical resolution and iii) asymmetric synthesis. Our recent syntheses of the following pheromones are included in this review : the yellow scale pheromone, lineatin, serricornin, and the pheromone of the saltmarsh caterpillar moth. Relationship between stereochemistry and pheromone activity is briefly summarized to show the complicated nature of pheromone perception.
Four germacranolide lactones 1, 1a, 2 and 2a were isolated from the underground parts of Ainsliaea acerifolia var. subapoda (Compositae). Their structures were determined by chemical and spectral studies. The structures should be represented by 1 : [1 (10) Z, 4E]-6βH, 7αH-germacra-1 (10), 4, 11 (13)-trien-12, 6-olide-14-O-β-D-glucopyranoside : 1a : [1 (10) Z, 4E]-6βH, 7αH-germacra-1 (10), 4, 11 (13)-trien-12, 6-olide-14-oic acid ; 2 : [4Z, 9Z]-6βH, 7αH-germacra-4, 9, 11 (13)-trien-12, 6-olide-14-O-β-D-glucopyranoside and 2a : [4Z, 9Z]-6βH, 7αH-germacra-4, 9, 11 (13)-trien-12, 6-olide-14-oic acid, respectively. Conformations of 1a and 2a were determined by nuclear overhauser effect studies. The spectral data for 1 (bitter principle), 1-tetraacetate (1c) and 1a were in agreement with the data for Taraxinsaure-1'-O-β-D-glucopyranoside (3), 3-tetraacetate (3b) and 3-hydrolyzate (3a), respectively. The new natural compounds 1a, 2 and 2a were named Taraxinsaure, ainslioside and ainsliolide, respectively.
Identification of photodegraded products of L-thyroxine (T4) suffering ultraviolet-(UV)-light irradiation (sterilization lamp 20 W, λmax 253.7 nm, radiation distance 40 cm) was carried out by gas chromatograph-mass spectrometer (GC-MS). N, O-Bis (trifluoroacetyl) methyl ester derivatives of authentic T4 and its related compounds and UV-light irradiated T4 samples were analyzed by GC-MS (JEOL JMS-D300 GC-MS and JEOL JMA-2000 Data Analysis System). Gas chromatography was carried out with a 1 m×2 mm column packed with 3% OV-17 and the temperature was programed from 100°C to 300°C with 10°C/MIN. Mass spectrometry was performed by electron impact ionization method at 70 eV. M+ was found to be measured in all compounds except L-tyrosine (Tyr) and the base peaks were shown at (M-113)+ for T4, L-3, 5, 3'-triiodothyronine (T3), L-diiodotyrosine (DIT), L-monoiodotyrosine (MIT), and at (M-184)+ for L-3, 3', 5'-triiodothyronine (3, 3', 5'-T3), L-3, 5-diiodothyronine (T2), L-3, 3'-diiodothyronine (3, 3'-T2), L-3', 5'-diiodothyronine (3', 5'-T2), L-3-monoiodothyronine HCl·H2O (3-T1), L-3'-monoiodothyronine (3'-T1), L-thyronine (T), Tyr. Individual derivatives gave single symmetrical peaks without tailing on their mass chromatograms. From the results of authentic compounds and of UV-light irradiated samples in mass spectra and mass chromatogram, T3, 3, 3', 5'-T3, T2, 3, 3'-T2, 3', 5'-T2, 3-T1, 3'-T1, T, DIT, MIT, and Tyr were identified as photodegraded compounds of UV irradiated thyroxine. We confirmed the degradated processes of thyroxine caused by UV-light irradiation. That is, the photodegradation liberated iodine at the first step and then cleaved the ether bond in the molecule, and finaly caused the liberation of α-phenyl ring on our experiment.
In order to know the biochemical evidence concerning structural characteristics of the lens, rat lens was incubated in the divided chamber which can separate anterior and posterior regions from each other, and the cataractogenic effects of ouabain, diamide, nigericin and ethylene glycol bis (β-aminoethylether)-N, N, N', N'-tetraacetic acid (EGTA) on Na+ and K+ contents in the lens were studied by adding these compounds either to the medium facing the anterior side or to the posterior side of the lens. Application of ouabain and diamide at the anterior side caused an increase of Na+ and a loss of K+, and the Na+/K+ value of this application was higher than that at the posterior side of the lens. In contrast, nigericin and EGTA caused cation changes independently of the side applied. These results may be related to the mode of action of such cataractogenic agents that the former two compounds act on lens by decreasing the activity of cation pump localized at the anterior surface of the lens, and the latter two compounds by increasing membrane permeability of cations.
To investigate the mechanism of senile cataract formation in human, detailed knowledge of biochemical changes occuring during opacification is first required. In the present paper, this subject is discussed in regards to opacity-related changes of cations, adenosine-5'-triphosphate (ATP) and glutathione, reduced form (GSH) in various types of human senile cataracts. Early cataract lenses had normal cation levels. However, when lenses were separated into nucleus and cortex, cation levels of the nucleus were higher than those of cortex in all stages of cataract. GSH level in lenses of the early cataract stage had already decreased, and its level in the anterior cortex region more decreased clearly compared with other regions of the mature cataract. ATP level in the lens decreased suddenly in the mature cataract. These results suggest that ATP levels are the same in all regions of the lens. In the nucleus during all stages of cataract, both GSH and ATP levels were always of a constant value. These levels were lower compared with other regions. Mg-ATPase maintained the same activity in the early cataract lens during all stages of cataract. However, Na, K-ATPase activity decreased remarkably in the immature cataract lens. These phenomena agreed with changes in the levels of Na+ and K+ during the cataract process. These results, when compared with those reported in our previous papers, illustrate the great difference in biochemical parameters of the human senile cataract by comparing it with the experimental cataract of animals. Taken together, these results, therefore, suggest the presence of many factors that may play a role during cataract formation in the human lens.
This paper describes differences in the adaptivity to the extraenvironment between two opaque situations in human cataract lenses after enucleation. The early and the premature cataract lenses of men were incubated in balanced salt solution containing 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) for three hours. The pH value of the medium containing the early cataract lens decreased more than that of the premature cataract lens. This pH value is correlated with increasing lactic acid production in the incubation medium from the cataract lenses. The early cataract lenses maintained normal cation level after three hours of incubation. However, the premature cataract lenses developed into mature cataract as a result of decreasing K+ and increasing Na+ levels. These results suggest that the early cataract lenses may retain normal metabolic activity in vivo, presumably due to normal levels of enzyme activities. In contrast, enzymatic activities in the premature cataract have already decreased. This short time incubation method may therefore be a useful means for monitoring the metabolic activity during various stages of the human cataract lens.
When slightly soluble medicinal crystals are administered orally, their particle size is one of the important factors affecting the bioavailability. Therefore, it was attempted to develop a new technique of particle size reduction, in which the addition of surfactants or polymers at crystallization was examined. In order to evaluate the size reduction effect for oxolinic acid (OA), the wet sieving method was studied by the use of the polycarbonate memblane filter. This method consists of the following procedures : 1) sonication of suspension more than 10 min, 2) suction filtration of suspension after dilution, 3) measurement of the weight of the residue on each filter by the determination of OA, 4) plots of the cumulative weight of residues on a log-probability paper, followed by calculation of apparent geometric mean diameter on weight basis, 5) regulation of the volume of filtrate according to the particle size of microcrystallines. It was found that the new method studied enabled to evaluate the size reduction effect easily and accurately.
The determination of drug concentration in the serum by laser immunochemical system (i-PiT) is a method based on the inhibition of immunoprecipitation by hapten (drug) when the antibodies can react with both hapten and polyhapten. We studied the i-PiT method using formalin to stop the antigen-antibody reaction after a regular reaction period, because of the fact that when the antibody is treated with formalin the reactivity is completely lost. At first, we investigated the formalin concentration in assay solution to inhibit the reaction completely and immediately after the addition of formalin. Consequently, we recognized that the reaction was inhibited almost completely at 35×14-1% of formalin, and more completely at 50×14-1%. Thus, commercial formalin as an inhibiting reagent was added into the assay solution to contain about 50×14-1% of formalin, the precision and accuracy of i-PiT method using formalin were studied in phenobarbital (PB) and phenytoin (PHT) assay. Hourly change, expressed as coefficient of variation, was less than 7.1%, and daily change for five days was less than 6.3% in PB and PHT assay. Mean recovery was 102.1% in PB assay, and 102.7% in PHT assay. The patients'serum specimens were analyzed, and the values correlated well to those determined by EMIT method. The coefficient correlation was 0.989 (n=37) for PB, and 0.980 (n=29) for PHT. In view of good precision and accuracy, i-PiT method using formalin was recognized as a useful method for the determination of PB and PHT in the serum.
The solubilities of the six phases (I, II, III-1/2 hydrate, IV, IV', V-hydrate) of cephalexin in distilled water were examined by the equilibrium method. Dissolution profiles of phase I, II, IV and IV'were almost the same profiles at each temperature, except those of phase I and IV'at 10°C. Transformation from phase I, II and IV'to phase IV was observed during solubility measurements at temperatures above 25.2°C, and transformation from phase I, IV and IV'to phase II below 25.2°C. The heats of solution for phase IV and II were calculated to be 1.63 kcal/mol and 0.068 kcal/mol, respectively, and the heat and entropy of transition were 1.56 kcal/mol and 5.23 e.u., respectively. The amount of crystals of phase III-1/2 hydrate dissolved in distilled water was at a maximum at the shaking time around 30 min at temperatures below 20°C. This finding is probably due to the transformation of the phase into phase IV at temperatures above 31.1°C, and into phase II at temperatures below 31.1°C. The heats of solution for phase III-1/2 hydrate and transformed into phase IV from phase III-1/2 hydrate were -6.38 kcal/mol and 1.75 kcal/mol, respectively, and the heat and entropy of transition were 8.13 kcal/mol and 27.1 e.u., respectively. The amount of crystals of phase V-hydrate dissolved in distilled water was at a maximum at the shaking time around 30 min at temperatures below 25°C. This finding is probably due to the transformation of the phase into phase IV at temperatures above 30.0°C, and into phase II at temperatures below 30.0°C. The heats of solution for phase V-hydrate and transformed into phase IV from phase V-hydrate were -1.23 kcal/mol and 2.61 kcal/mol, and the heat and entropy of transition were 3.84 kcal/mol and 10.8 e.u., respectively.
The effect of atropine on the gastrointestinal absorption of sulfisomidine was investigated in rabbits. Atropine reduced the maximum blood concentration (Cmax) of sulfisomidine, and prolonged the time taken to reach the maximum blood concentration (Tmax) of sulfisomidine. However, atropine had no effect on the area under blood concentration-time curve (AUC) and the elimination half-life (t1/2) of sulfisomidine. In addition, atropine delayed the gastric emptying rate, but did not change the dissolution rate and the intestinal membrane permeability of sulfisomidine. These results led us to conclude that atropine affects the rate but not the extent of the gastrointestinal absorption of sulfisomidine, by delaying the gastric emptying rate.
The degradation rates of penicillins and cephalospolin C's in aqueous solution were found to be accelerated by the coexistence of sodium bisulfite (SBS). The action of SBS was recognized to be catalytic. The destructive actions of SBS on penicillin G, carbenicillin, methicillin and sulbenicillin were shown by comparatively small catalytic rate constants. The actions of SBS on ampicillin and cloxacillin were shown by one figure larger catalytic rate constants, i.e., catalytic rate constants for penicillin G and ampicillin were 4.47 M-1h-1 and 30.53 M-1h-1, respectively, at 60°C, pH 6.5 and μ=0.1. The degradations of cephaloridine and cephalothin were also remarkably accelerated by SBS. As the results of stability studies on ampicillin in solution, the action of SBS was shown to be largest at pH value of approximately 6.5 and pH-rate profile was known to be inverse to that of the straight solution of ampicillin, and the effects of temperature and the concentration of SBS on the actions were determined. By utilizing these data, a new practical approach by use of a nomograph was proposed to predict the stability of ampicillin in the admixture of the antibiotics with parenterals containing SBS as an additive.
In order to examine whether or not an acyl group in diacyl peroxide is exchanged by another one, like transacylations in esters and in acid anhydrides, the reaction of acetyl benzoyl peroxide with acetic acid in the presence of sulfuric acid was carried out at 45°C for 5 h. Perbenzoic acid and acetic anhydride were formed as reaction products. Propionyl benzoyl peroxide was found in the reaction of acetyl benzoyl peroxide with propionic acid. Therefore, transacylation of the diacyl peroxide was confirmed.
A capillary-tube isotacophoretic procedure for the determination of valproic acid was established. Valproic acid was separated with the following mobile ions : leading electrolyte, 2.5 mM hydrochloric acid in 0.2% polyvinylalcohol adjusted to pH 5.50 by adding L-histidine ; terminating electrolyte, 2.5 mM 2-(N-morpholino) ethanesulfonic acid solution adjusted to pH 7.20 with tris (hydroxymethyl) aminomethane. Commercially available preparations of sodium valproate were determined without pretreatment such as the extraction with organic solvent and the derivation. The values of valproic acid determined by the method were in good agreement with those determined by gas-liquid chromatographic method. This method provides a simple and rapid technique for the determination of valproic acid.
Studies were made on the biological activity of ten 9-diethylaminobenzo [α] phenoxazonium salts (BPZ). (1) 9-Diethylaminobenzo [α] phenoxazonium nitrate (1) was found to have a high antitumor effect on Ehrlich carcinoma. (2) 1 and 9-diethylamino-5-phenylsulfonylbenzo [α] phenoxazonium nitrate (2) were found to have some antitumor effects on RADA 1 Leukemia cell. (3) 9-Diethylamino-5-(3-methylphenylthio) benzo [α] phenoxazonium nitrate (9), 9-diethylamino-5-(4-methylphenylthio) benzo [α] phenoxazonium nitrate (10), 9-diethylamino-5-phenylthiobenzo [α] phenoxazonium nitrate (4) and 9-diethylamino-5-(2-methylphenylthio) benzo [α] phenoxazonium nitrate (8) were found to show some antibacterial effects on Staphylocoocus aureus 209 P.