This review describes a total synthesis of natural products by "Retro Mass Spectral Synthesis"developed in our laboratory. This method is an effective way of analysis for designing synthetic routes by applying the retro-process of mass spectral fragmentation.
The methylation of pyrazine with methanol was carried out in the presence of Ni catalysts. Raney Ni was found to have an excellent activity for the methylation and 2-methylpyrazine was formed as a main product, with a small amount of dimethylpyrazine. By use of Raney Ni at 200°for 12hr, the yields of 2-methylpyrazine and dimethylpyrazine were 49.2 and 9.3%, respectively. Pyridine was also methylated with Raney Ni in good yield. The activity of several types of Ni catalysts was examined in the methylation of pyrazine.
In a mixed electrolyte solution, the ionic flux through the membrane is driven not only by a concentration gradient, but also by an electric potential gradient. Therefore, reverse permeation of an ion can occur, which means permeation against the concentration gradient, and also overshooting can occur, which means permeation beyond the equilibrium concentration. We have already revealed these phenomena both theoretically and experimentally. In this paper we defined the electric potential gradient by each ion, (∂E/∂x), and the flux by a concentration gradient, JIC, and the flux by an electric potential gradient by each ion, JiEj, in order to reveal the driving force on the reverse permeation or on the overshooting. We analysed the results of permeation through the cellulose membrane on HCl-KCl-H2O and HCl-CaCl2-H2O ternary systems. It was concluded that reverse permeation could occur when the ionic flux by electric potential gradients of coexisting ions was reverse in the direction and large enough, because the electric potential gradient of the ion which does reverse permeation was very small. And it was also concluded that overshooting could also occur when the ionic flux by coexisting ions was the same in the direction and large enough upon the concentration reaching the equilibrium value. We discussed the condition of overshooting precisely.
Two new eremophilane derivatives, α, α'-bis (3β-angeloyloxyfuranoeremophilane), 3β-angeloyloxy-8β-hydroxy-9β-senecioyloxyeremophilenolide were isolated from the rhizome of Farfugium japonicum (L.) KITAM. (Ligularia tussilaginea MAKINO), along with α-amyrin, campesterol, stigmasterol, β-sitosterol, palmitic acid, linoleic acid and linolenic acid. From the leaves of this plant above-mentioned phytosterols and brein were obtained.
3-Benzylamino- and 3-morpholinocrotonamide (8 and 9) reacted with diketene to give the corresponding 6-methyl-2-pyridone derivatives (23 and 24), respectively. The reaction of N-methyl-3-morpholinocrotonamide (11) and N-benzyl-3-benzylaminocrotonamide (12) with diketene afforded the corresponding pyrano [3, 2-c] pyridine-2, 5-dione derivatives (27 and 28). The reaction of N-benzyl-3-morpholinocrotonamide (13) with diketene gave 8-acetyl-6-benzyl-6, 7-dihydro-2, 5-dimethyl-4H-pyrano [3, 2-c] pyridine-4, 7-dione (29). On the other hand, 3-aminocrotonanilide derivatives (14-19) reacted with diketene to give 2-pyridones (30, 32, 35, 37, 39) and 4-pyridones (34, 36, 38, 40). The reaction of 3-morpholinocrotonanilides (20-22) with diketene to give the corresponding 3-carbamoyl-4-pyrone derivatives (41-43) is also described.
The levels of individual phospholipids-total phospholipids (TPL), lysophosphatidylcholine (LPC), sphingomyelin (Sph) and phosphatidylcholine (PC) were determined in serum samples from 14 healthy adults and 32 patients with malignant tumor including 9 gastric cancers and 9 lung cancers. Additionally, the activities of lecithin : cholesterol acyltransferase (LCAT) were measured in the same samples from 7 healthy adults and 2 patients with lung cancer. The levels of LPC and PC were shown significantly lower in the patients with malignant tumor than those in healthy adults. But no differance was found in the level of Sph. In the patients with malignant tumor, serum LPC level was very markedly lower than that in the healthy adults, though there was no difference in the serum LCAT activity between the patients and healthy adults.
Ammonia adduct formation was confirmed in 5 sulfonylureas including acetohexamide, glyclopyramide, chlorpropamide, tolazamide, and tolbutamide. The thermal and physico-chemical properties of these adducts and the recovered chemicals were investigated by differential scanning calorimetry, thermogravimetry, thermomicroscopy, X-ray powder diffractometry, and scanning electron microscopy. From the specific surface area measurement by a gas adsorption (BET) method, it was found that effective particle size reduction was achieved with sulfonylureas recovered by desorbing NH3 from the adducts. Further, the effect of particle size on the temperature range of melting and the heat of fusion was investigated with glyclopyramide, tolazamide, and tolbutamide. It was found that, in spite of the same purity, the melting peaks of size-reduced particles via these NH3 adducts became sharper but shifted to lower temperature and the heats of fusion were smaller than those of the original sulfonylureas.
From the ether-soluble fraction of aqueous extract of the roots of Stellaria dichotoma L. var. lanceolata BGE., a mixed compound of α-spinasterol and stigmast-7-enol, its palmitate, furan-3-carboxylic acid and a flavone derivative, wogonin were isolated.
From the fruits of Angelica pubescens MAXIM. (Umbelliferae), nine coumarins, osthol (1), byak-angelicin (9), ferulin (14), oxypeucedanin (15), umbelliferone (16), umbelliprenin (17), imperatorin (18), neobyakangelicol (19), 5-methoxy-8-(2-acetoxy-3-hydroxy-3-methylbutoxy) psoralen [sec-O-acetylbyakangelicin] (20) were isolated. The major component 17 was isolated for the first time from the plants growing in Japan.
Chromogenic method was examined for simple and quick determination of the activities of amylases in gastrointestinal drugs. The synthetic chromogenic substrates from Cibachron Blue 3GA, various amyloses and starches were employed in this experiment. Commercial chromogenic substrate, Amylochrome Roche, had the most superior reactivity to the synthetic Cibachron Blue 3GA-amyloses or starches. α-Amylase, endo type glucan hydrolase, had very high activity, but β-amylase and amyloglucosidase, exo type glucan hydrolase, had no activity towards the chromogenic substrates. So it suggested that this method was α-amylase specific. The activity of amylase in gastrointestinal drugs was determined simply and quickly by this method. It can be useful for the routine quality control of the gastrointestinal drugs.
Rice bran lectin (RBL) agglutinated human erythrocytes regardless of their ABO and MN blood-group systems. The receptor activity of erythrocytes against RBL was completely abolished by treatment with pronase for two hours and partially abolished by treatment with trypsin or α-chymotrypsin for three hours. Sialoglycopeptides released from human erythrocytes by treatment with protease such as pronase, trypsin or α-chymotrypsin inhibited the hemagglutination by RBL. Removal of sialic acid residues of sialoglycopeptides diminished their inhibitory activities. Among sugars tested, only N-acetyl-D-glucosamine showed hemagglutinating inhibition.
Serum digoxin levels (SDL) have been known to be a good indicator for digitalis intoxication since radioimmunoassay (RIA) of serum digoxin level became available. To apply pharmacokinetics and RIA of digoxin to the routine practice of medicine, a new method of estimating digoxin blood levels at steady state was evaluated. Blood digoxin concentration in a blood sample obtained at transition state or 3-6 days after initial dosage was used for the estimation of digoxin level at steady state. The apparent volume of distribution was calculated by using multiple dosing equations based on open linear one compartment model. Phadebas RIA stat assay kits were used for the rapid measurement of serum digoxin levels. In six hospitalized patients receiving oral dose of digoxin (0.125-0.25mg per day), estimated digoxin levels at steady state were compared with the values measured by RIA. The estimated and measured values agreed well with a slight discrepancy ranging from 1.5-13% (m^-=6.8%). The method may prove useful as the practical means of predicting SDL at steady state, which allows assessment of digoxin therapy and change of the regimen, if necessary, before intoxication occurs.
Antidiabetic activity of Chinese prescription "Hachimi-Gan"was studied by using diabetic rats induced by streptozotocin. Changes in water consumption, urine volume, blood and urinary glucose were studied in order to examine the activity. "Hachimi-Gan"exhibited the antidiabetic activity, while the boiling water extract of "Hachimi-Gan"was ineffective. Among the components of crude drugs of "Hachimi-Gan, "the ether extract of Corni Fructus (The seed of Cornus officinalis) was found to be potent for these diabetes rats. Fractionation of the ether extract revealed that ursolic acid showed the antidiabetic activity and oleanolic acid decreased the amount of water consumption and urine volume.
Preliminary examination of antitumor screening of 20 nitrofuran derivatives was carried out with mice bearing Ehrlich ascites tumor. Among these comounds, 2-[β-(5-nitro-2-furyl) ethynyl]-furan (1) and 3-(5-nitro-2-furyl)-2-phenyl-quinoxaline 1, 4-dioxide (14) exhibited a fair antitumor activity.
cis-1-Thioniabicyclo [4. 4. 0] decane bromide (cis-TBD-Br) and its trans isomer, both having distinctly different crystal modifications at room temperature, are transformed into the same crystalline modifications (α-phase) at high temperatures. An infrared absorption analysis carried out at 175°indicates that the α-phase contains both the cis-TBD and trans-TBD rings as its constituents approximately in the ratio 3 : 2. The lattice constants of the α-phase at 175°containing four formula units, C9H17SBr, are a=13.09, b=10.09, c=8.44 A. The space group corresponds to one of Fmmm, Fmm2 and F222. It is concluded that the two kinds of the isomeric ring ions are distributed statistically around four equivalent positions having a site symmetry (mmm, mm 2 or 222) given by the space group so that these ions should have statistical orientations. At room temperature, it decomposes gradually into its component crystals, cis- and trans-TBD-Br, but can be kept for several days in a desiccator over silica gel.