Stable carbocations do not react with non-activated benzenes. The electrophiles, which can react with benzene, are reactive carbenium ions substituted with a genuine electron-withdrawing group (>C+-X), wherein the substituent X represents carbenium, oxonium, ammonium, O-protonated hydroxylamino, O-protonated N, N-dihydroxylamino, and trifluoromethyl. Experimental evidence, including spectroscopic ones, demonstrated the involvements of these cationic species as discrete reaction intremediates.
Hydrophobic cyclodextrin (CyD) derivatives, such as 2, 6-di-O-ethyl-β-CyD (DE-β-CyD), 2, 3, 6-tri-O-ethyl-β-CyD (TE-β-CyD), carboxymethylethyl-β-CyDs (CME-β-CyDs) with different degrees of substitution, 2, 3, 6-tri-O-acyl-β-CyDs with different alkyl chains (C1-C12) were prepared and their chemical structures and physicochemical properties were elucidated. Furthermore, possible utilities of hydrophilic and hydrophobic CyD derivatives as modifiedrelease drug carriers were evaluated on the basis of in vitro/in vivo correlations. The results obtained in this study are as follows : (1) Hydrophilic CyDs such as 2-hydroxypropyl-β-CyD are useful as immediate-release type carriers for poorly water-soluble drugs such as nifedipine. (2) Hydrophobic CyDs such as ethylated and acylated β-CyDs can be used as prolongedrelease type carriers for water-soluble drugs such as diltiazem hydrochloride, buserelin acetate and molsidomine. (3) Enteric CME-β-CyD derivatives are useful as delayed-release type carriers, and also as stabilizers for prostaglandin E and carmofur which are labile under alkaline conditions. (4) Various release rates can be obtained by combining hydrophilic and hydrophobic CyD derivatives in appropriate mixing rations, e.g., double-layer tablets consisting of β-CyD complex and DE-β-CyD/CME-β-CyD complexes released drugs rapidly at an initial stage, followed by slow release. The combination of CyD derivatives and pharmaceutical additives was also useful to modify the release rate of various drug molecules.
A 1, 3-polyhydroxylated chain is often found on the backbone of biologically important natural products. The acyclic nature and the regular array of many hydroxyl groups are main obstacles to structural and synthetic studies, and many efforts have been made to this end. We have developed a new general synthetic method of 1, 3-polyols based on the coupling of a chiral dithiane, a four-carbon unit, and an epoxide, followed by 1, 3-diastereoselective reduction. We applied the method to the synthesis of polymethoxy-1-alkenes isolated from blue-green algae to establish their absolute stereochemistry. Moreover, a general procedure for assigning the absolute stereochemistry of acyclic 1, 3-polyols by the difference circular dichroism (CD) method have been established. Combination of the method and a reiterative degradation enables one to determine the absolute configuration of 1, 3-polyols, even if the relative stereochemistry is unknown.
In order to elucidate the structure-activity relationship between the antitumor activity and the molecular structure of novel DNA-intercalator acridine derivatives (1a-g and 2a-i in Chart 1), DNA-binding properties (intercalation) of these acridines were examined by quenching in the fluorescence of the ethidium-DNA complex. The mechanism of quenching is caused by the displacement of DNA-bound ethidium by a second DNA binding ligand, acridines. The concentration (C50 value) of acridine necessary to reduce the initial fluorescence of DNA-bound ethidium by 50% showed a good correlation with their antitumor activities. The quenching of fluorescence for acridines was examined using amsacrine (AMSA) as a typical standard of the second DNA-bound ligand, and calf thymus DNA with an apparent site size of two base pair. Some of the acridine derivatives showed more potent quenching of fluorescence than amsacrine (AMSA).
In order to evaluate the utility of far-infrared drying method for crude drugs, the efficiency in the drying process of Ginseng Radix and Ginseng Radix rubra was examined. Furthermore, chemical fluctuation of the constituents of Ginseng Radix and Ginseng Radix Rubra, which may occur during their drying process, has been investigated by means of HPLC quantitative analysis for ginsenosides and malonyl-ginsenosides, and TLC qualitative analysis for lipophylic constituents. It has been found that the far-infrared drying method (oven temperature 45°C) dried Ginseng Radix faster without reducing both ginsenosides and malonyl-ginsenosides in comparison with the conventional drying methods such as an air drying and a hot-air drying.