Axially chiral monophosphines, 2-(diphenylphosphino)-1, 1'-binaphthyl (MOPs, 1) were prepared starting with homochiral 2, 2'-dihydroxy-1, 1'-binaphthyl. The palladium complexes coordinated with the MOP ligands are highly effective catalysts for several types of catalytic asymmetric reactions where chelating bisphosphine ligands can not be used because of their low catalytic activity or low selectivity towards the desired reaction pathway. Typical examples of the catalytic asymmetric reactions are as follows : 1) Asymmetric hydrosilylation of alkyl-substituted terminal olefins and bicyclo [2.2.1] heptene derivatives giving, after oxidation, optically active alcohols (up to 98% ee). 2) Asymmetric reduction of allylic esters with formic acid (up to 93% ee).
LC/MS is now considered to be the most promising analytical method for the determination of biological substances, especially nonvolatile or high molecular weight substances. But one of the drawbacks of this method is its low sensitivity in comparison with GC/MS. In order to overcome this problem, the derivatization methods are used in LC/MS. This report overviews the detection-oriented derivatization methods in LC/MS including our results. The typical examples are as follows. The derivatization of vitamin D with a Cookson-type reagent (analog of 4-phenyl-1, 2, 4-triazoline-3, 5-dione) gave satisfactory sensitivity, which was also observed on the derivatization of oxosteroids with O-methylhydroxylamine. Although the oxosteroid fatty acid esters gave a de-esterified ion as a base peak in atmospheric pressure chemical-ionization MS, the methyloxime of which gave a quasimolecular ion as a base peak, which is helpful to identify the compounds in the brain.
The effects of beclomethasone dipropionate (BDP) enemas on ulcerative colitis were investigated by administrating BDP enemas to Fischer male rats with an inflammatory bowel disease induced by 2, 4, 6-trinitrobenzensulfonic acid (TNB). After administration of a TNB ethanol solution to rats, diarrhea and melena were found in all rats, and the wet tissue weights of the colons in the rats increased by erosion and thickness of epithelial mucous membranes with edema. BDP enemas were administered to the rats one time a day at a dose of 20 or 50 μg of BDP for 4 or 11 days from the day 3 after TNB treatment, respectively. After dosing of BDP, the rate of rats developing diarrhea and melena decreased more with time in comparison with that of BDP-free rats, and the symptoms of all rats developing the diseases were improved on the day 4 after administration of a dose of 50 μg of BDP. A dose dependent recovery in the wet tissue weights and scores of damages, and the myeloperoxidase (MPO) activity in the tissue were found at the early days (until the day 4). However, their measurements on the day 11 at each dose of BDP were not different from those of control rats significantly, as the damages in the colons of the control rats were recovered naturally with time. In conclusion, the clinical usefulness of BDP enemas was supported by elucidating the dose dependent effect of BDP at the early days in the model rats with an inflammatory bowel disease induced by TNB.
As the continuation of the work on the antioxidant properties of furan derivatives, we have studied hydroxyl radical (OH·) scavenging activity of dimethylfuran (DMF) and diphenylfuran (DPF), which are well-known as an effective scavenger of singlet oxygen, by an ESR spin trapping technique. The incubation mixture of 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trapping agent with Fe<2+> and H2O2 in 50% acetonitrile aqueous solution gave 1 : 2 : 2 : 1 line signals characteristic of DMPO-OH spin adduct. The additions of furan derivatives to the incubation mixture decreased the intensity of the DMPO-OH spin adduct signal in a dose-dependent manner. The activities of furan derivatives were in the order of DMF > DPF > furan. The decrease in the intensity of the signals was not due to the inhibition of OH· generating system itself and the destruction of the spin adduct by furan derivatives. By comparison with the common OH· scavengers, DMF and DPF were found to scavenge OH· more effectively than dimethylsulfoxide and mannitol. These results indicate that DMF and DPF can act as a OH· scavenger as well as a singlet oxygen scavenger.
Lumbricus has been widely used as an antifebrile agent in cold medicines. The identification of each agent, especially crude drugs in formulations, is very important from the viewpoint of quality control. In this paper, the contents of amino acids, organic acids, nucleic acid components and cholesterol were investigated to evaluate the "signal" constituents of Lumbricus and Lumbricus extracts in the medicines. It was found that the content pattern of these components of Lumbricus extracts was almost the same as those in Lumbricus itself. However, most of other crude drugs used in cold medicines, also contain some of these components. It was difficult to identify Lumbricus through the difference in the content pattern of these components. Therefore, we focussed on such five constituents as cholesterol, lombricine, lactic acid, inosine and hypoxanthine, because lombricine is a characteristic amino acid of Lumbricus and the contents of other four components in Lumbricus are relatively high compared with those of other crude drugs. Lombricine and inosine were detected clearly in all seven commercial formulations investigated, and cholesterol and hypoxanthine were also detected except two commercial formulations. However, the detection of lactic acid was not successful in all formulations, because of the presence of interfering components. In the seven commercial cold medicines, lombricine and inosine were found to be useful as "signal" constituents for the identification of Lumbricus in cold medicines.
We have investigated the effects of Shimotsu-to, a traditional Chinese herbal prescription (Kampo medicine), on ultraviolet (UV) radiation-induced cell damage and prostaglandin E2 (PGE2) release in cultured Swiss 3T3 cells to examine the anti-inflammatory mechanism of Shimotsu-to. Short-term UV irradiation significantly induced cell damage and stimulated PGE2 release in Swiss 3T3 cells cultured for 4 h. The UV-radiation-induced cell damage and the stimulation of PGE2 release were significantly suppressed by the treatment with Shimotsu-to. Among the single crude drug components of Shimotsu-to, Rehmanniae Radix showed significant protective effects against UV-radiation-induced cell damage and PGE2 release. Other synthetic anti-inflammatory agents, such as dexamethasone, dipotassium glycyrrhizinate and allantoin also protected against UV-induced cell damage and inhibited PGE2 release in cultured Swiss 3T3 cells. These results suggest that the anti-inflammatory mechanism of Shimotsu-to against UV-irradiated erythema (acute skin inflammation) in guinea pigs in vivo may be mediated by the inhibition of PGE2 release from cutaneous target cells.
We investigated the large scale synthesis of monocalcium bis [(2S)-2-benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl)propionate] dihydrate (KAD-1229), which has a potent hypoglycemic effect, in a single reaction vessel. (2S)-2-Benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl)propionic acid (7) was directly obtainable from (S)-2-benzylsuccinic acid (2) and cis-hexahydroisoindoline (4), without the isolation of intermediates by the method using thionyldiimidazole (9) and/or diimidazolide of the acid 2. Sequential reaction of imidazole with thionyl chloride, 2, and 4, followed by acid catalyzed hydrolysis gave amidecarboxylic acid 7 in 86% overall yield. The acid 7 was treated with 2N NaOH, followed by the treatment with calcium chloride to give KAD-1229 in 91% yield.