Application of overpressured layer chromatography combined with digital autoradiography and mass spectrometry in the study of deramciclane metabolism.

Overpressured layer chromatography was combined with the highly sensitive and rapid digital autoradiography (DAR) and mass spectrometry to separate, detect, and identify 3H- and 14C-labeled deramciclane metabolites in different biological matrixes. Several minor and major metabolites were separated from plasma and urine samples. The radioactive metabolites localized by DAR were scraped from the thin-layer chromatographic plate and transferred to a mass spectrometer for structure identification. Several metabolites were isolated and characterized, including hydroxy-N-desmethyl deramciclane, which is described in detail. The combination of techniques is efficient and has good sensitivity: about 2 micrograms metabolite from a biological matrix was isolated and identified this way.

[Additional data from the NMR investigation of tofizopam]. / Adatok a tofizopam NMR spektroszkópiai vizsgálatához.

The seven-membered ring of Tofizopam exists in two stable conformations in solutions. Separately detectable (Et)Me triplets of the conformers offered us a way for quantitative determination of conformer ratios. Temperature dependence of free enthalpy of conformers were calculated from the measured conformer ratios in different temperatures. Entropy component of the free enthalpy proved to be 35% of the whole at 36 degrees C. Half period of attaining equilibrium ratio of conformers was 2 hours at 36 degrees C.

cis-trans-isomerization of [E]-5-(2-bromovinyl)-2,2'-anhydrouridine in vivo in rats.

1. [E]-5-(2-bromovinyl)-2,2'-anhydrouridine [( E]BVANUR) has considerable antiviral activity against herpes simplex virus type 1 (HSV-1). 2. [E]BVANUR is not a substrate of pyrimidine nucleoside phosphorylases, but it is an inhibitor of uridine phosphorylase (Ki = 450 nM). 3. [E]BVANUR (trans-isomer, parent compound) undergoes isomerization to [Z]BVANUR (cis-isomer), the only metabolite in rat, which was identified by h.p.l.c., mass spectra and n.m.r. spectroscopy. 4. Absorption of the drug from the gastrointestinal tract after oral administration is minimal. Absorption of [E]BVANUR from the abdominal cavity after i.p. administration was slow.

Biological activity of the potent uridine phosphorylase inhibitor 5-ethyl-2,2'-anhydrouridine.

5-Ethyl-2,2'-anhydrouridine (ANEUR) proved to be a potent inhibitor of uridine phosphorylase isolated from sarcoma 180 cells with an apparent Ki (Ki(app) value of 99 nM. Coadministration of ANEUR with 5-fluorouridine (FUR) resulted in increased toxicity of FUR. The LD50 value of FUR alone was 9 mg/kg (when administered for 5 consecutive days) while the LD50 was 3 mg/kg when FUR was administered together with ANEUR in vivo. There was no significant difference in mean tumor weight on day 10 between control animals and animals treated with FUR (5 mg/kg/day for 3 days) or ANEUR (280 mg/kg/day for 3 days). When FUR was coadministered with ANEUR, mean tumor weight was 91% less than that of the untreated controls, showing that ANEUR, the potent URPase inhibitor, increases the antitumor effect of FUR.

N-substituted trimethylsilylcarbamates as silylating and/or methoxime derivatizing reagents for gas chromatographic analysis.

N-Substituted trimethylsilylcarbamates were tested as derivatizing reagents for gas chromatographic analysis. N,N-Dimethyltrimethylsilylcarbamate was found to be a suitable agent for direct trimethylsilylation of the salts of alkaloids without previous liberation of the bases. N-Methoxy-N,O-bistrimethylsilylcarbamate was found to react simultaneously and quantitatively with the hydroxy and keto groups of steroids, resulting in the corresponding methoxime trimethylsilyl derivatives.

Griseochelin, a novel carboxylic acid antibiotic from Streptomyces griseus.

Griseochelin, C33H60O7, isolated from an asporogenous strain of Streptomyces griseus represents a novel carboxylic acid antibiotic. The metabolite, which is active against Gram-positive bacteria, forms water-insoluble salts with mono- and divalent cations and binds alkaline-earth metal ions specifically in 2:1 (X2M) stoichiometry. Detailed spectral (IR, MS and NMR) studies provide full characterization of its constitution featuring a carboxylic acid function, a substituted tetrahydropyran ring, an allylic OH group which are accommodated within a tetrahydroxylated-octamethyl-C25 diene backbone.