Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives. II. 6-Alkyl- and 6-cycloalkylalkyl derivatives.

A series of 6-alkyl- or 6-(cycloalkylalkyl)-[1,3,4]thiadiazolo[3,2- a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-ones 1b--o was synthesized from the corresponding 1,3,4-thiadiazol-5-amines 3b--o and the antiallergic activities of the products were evaluated. Among the compounds 6-(2-cyclohexylethyl)- [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one 1h, whose X-ray crystallographic stereostructure is shown, was found to be a promising new antiallergic agent, which has low toxicity and dual activity as a leukotriene D4 receptor antagonist and as an orally active mast cell stabilizer.     

Structure of an anti-plasmin inhibitor, eckol, isolated from the brown alga Ecklonia kurome Okamura and inhibitory activities of its derivatives on plasma plasmin inhibitors

Eckol (1), a novel phlorotannin with a dibenzo-1,4-dioxin skeleton, has been isolated from the brown alga Ecklonia kurome Okamura as a potent and specific anti-plasmin inhibitor. Its structure has been elucidated based on the spectral data, in particular, by means of negative nuclear Overhauser effect (NOE), and finally established as 1-(3,5-dihydroxyphenoxy)-2,4,7,9-tetrahydroxydibenzo-1,4-dio xin by X-ray analysis. Some partially methoxylated derivatives of eckol were prepared by methylation with diazomethane and also by selective dimethylation of eckol permethylate (1b) to establish the structural requirements for inhibitory activities on alpha 2-macroglobulin and alpha 2-plasmin inhibitor, the main plasmin inhibitors in plasma.     

Effects of photo-activated bleomycin on deoxyribonuclease I, exonuclease III and deoxyribonucleic acid polymerase I reactions

The activity of bleomycin to break the strand of deoxyribonucleic acid (DNA) in the presence of 2-hydroxy-1-ethanethiol (2-mercaptoethanol) was enhanced by ultraviolet (UV) irradiation. Photo-activated bleomycin stimulated the action of deoxyribonuclease I (DNase I) to degrade DNA and the DNA synthesis by DNA polymerase I with DNase I. On the other hand, although UV-irradiated bleomycin scarcely broke the DNA strand in the presence of 1,2-benzenediol (catechol), it stimulated the action of DNase I to degrade DNA in the presence of catechol. In accordance with the inhibition by catechol, when DNA treated with UV-irradiated bleomycin in the presence of catechol was employed as a primer for the DNA synthesis, the incorporation of precursor into the acid-insoluble fraction by DNA polymerase I with exonuclease III was reduced to about one-half of the incorporation into DNA treated with unirradiated bleomycin. These findings suggest that the ability of bleomycin to bind to double-helical DNA forming regions sensitive to DNase I was increased by an appropriate dose of UV irradiation and that catechol inhibited the activity of the UV-irradiated bleomycin to break the DNA strand rather than to bind to DNA.     

Quantitative determination of benzalkonium chloride in treated wood by solid-phase extraction followed by liquid chromatography with ultraviolet detection

Ammoniacal copper quat (ACQ) compound wood preservative is comprised of copper and quaternary ammonium compounds with benzalkonium chloride (BAC) as the active ingredient. Solid-phase extraction (SPE) followed by liquid chromatography with ultraviolet detection (LC-UV) was developed for quantitative determination of BAC in treated wood. Five species of wood were used, Japanese cedar (Cryptomeria japonica), Japanese larch (Larix leptolepis), Yezo spruce (Picea jezoensis), Sakhalin fir (Abies sachalinensis), and western hemlock (Tsuga heterophylla). BAC used in the present study was composed of 66% C12, 33% C14 and less than 1% C16. BAC was added to each wood species (500 mg) then extracted with HCl-ethanol (20 ml) and quantitatively determined with LC-UV (262 nm). Wood extractives from the heartwood of each species, except western hemlock, interfered with quantitative determination of BAC, but SPE with an Oasis MCX cartridge was effective in preventing this. Using the present methods, BAC homologue peaks were clearly confirmed without interference. Recoveries from wood ranged from 92 to 101% and the limit of quantitation was approximately 240 microg/g wood for the C12 and C14 homologues.     

Requirement for radiation shields of transportation pipe for on line inhalation gases from compact cyclotron in positron emission tomography

In the unit housing of a compact cyclotron and positron emission CT (PET), positron emitting gas such as 15O, 11C, C15O2, C15O etc. is supplied from a cyclotron to a PET room through a transportation pipe with an appropriate shield to reduce positron annihilation radiation. Using lead or concrete shield blocks with various thicknesses, radiation leakage through the shield was measured by an ionization chamber type survey meter during continuous and constant supply of 15O gas of 1.85 GBq/min concentration which is the maximum dose for clinical use. The leakage radiation measured was 213.7, 56.0, 15.3, 5.0 muSv/week for lead shield with 1, 2, 3, and 4 cm thickness, respectively, and 193.3, 30.5 and 5.1 muSv/week for concrete shields with thickness of 10, 20, and 30 cm, respectively. The present study shows that to keep less than 300 muSv/week, which is the permissible dose rate of the boundary zone around the radiation controlled area by Japan Science and Technology Agency, it is required to use more than 8 mm thick lead shield or 7 cm thick concrete for continuous supply of 1.85 GBq/min 15O gas.     

Simple and sensitive determination of methylglyoxal in biological samples by gas chromatography with electron-capture detection

Methylglyoxal was allowed to react with 4,5-dichloro-1,2-phenylenediamine, and the 6,7-dichloro-2-methylquinoxaline formed was determined by gas chromatography with electron-capture detection. The standard curve of the quinoxaline was linear up to 160 pmol/ml. The recoveries of methylglyoxal from coffee and rat liver homogenate were 84.1 and 77.6%, respectively. This procedure was very selective and so sensitive that as little as 9 fmol of the quinoxaline could be measured in biological and food samples.     

Ion-exclusion chromatography with conductimetric detection of aliphatic carboxylic acids on a weakly acidic cation-exchange resin by elution with benzoic acid-beta-cyclodextrin

In this study, an aqueous solution consisting of benzoic acid with low background conductivity and beta-cyclodextrin (beta-CD) of hydrophilic nature and the inclusion effect to benzoic acid were used as eluent for the ion-exclusion chromatographic separation of aliphatic carboxylic acids with different pKa values and hydrophobicity on a polymethacrylate-based weakly acidic cation-exchange resin in the H+ form. With increasing concentration of beta-cyclodextrin in the eluent, the retention times of the carboxylic acids decreased due to the increased hydrophilicity of the polymethacrylate-based cation-exchange resin surface from the adsorption of OH groups of beta-cyclodextrin. Moreover, the eluent background conductivity decreased with increasing concentration of beta-cyclodextrin in 1 mM benzoic acid, which could result in higher sensitivity for conductimetric detection. The ion-exclusion chromatographic separation of carboxylic acids with high resolution and sensitivity was accomplished successfully by elution with a 1 mM benzoic acid-10 mM cyclodextrin solution without chemical suppression.     

Synthesis of all of the four possible stereoisomers of pestalotin,a gibberellin synergist isolated from pestalotia cryptomeriaecola sawada

(-)-Pestalotin [(6S, l'S)-6-(1'-hydroxypentyl)-4-methoxy-5,6-d dihydro-2-pyrone 1a]and its three other stereoisomers were synthesized either by utilizing the Sharpless asymmetric epoxidation as the keystep or by derivation from D-(+)-glyceraldehyde acetonide.     

Ferromagnetic anomaly associated with the antiferromagnetic transitions in (donor)[Ni(mnt)2]-type charge-transfer salts

Three newly prepared [Ni(mnt)2] complexes, (HMTTF)[Ni(mnt)2], (ChSTF)[Ni(mnt)2], and (DBTTF)2[Ni(mnt)2], are reported (DBTTF = dibenzotetrathiafulvalene, ChSTF = 2,3-cyclohexylenedithio-1,4-dithia-5,8-diselanafulvalene, HMTTF = bis(trimethylene)-tetrathiafulvalene, and mnt = maleonitrile dithiolate). The former two compounds have usual DA-type (D = donor, A = acceptor) mixed stacks, whereas the DBTTF complex has DDDDAA-type 6-fold columns. These compounds are electrical insulators, but the HMTTF and ChSTF complexes exhibit chiT minima at 16 and 55 K, respectively, followed by chiT peaks at 8 and 16 K. Below these temperatures the ESR signal disappears, indicating antiferromagnetic transitions. The origin of the ferromagnetic interaction is explained either from the difference of the g values between the donor and the anion or from the intrinsic ferromagnetic interaction of the [Ni(mnt)2] anions.