Gas chromatography-mass spectrometry of monohydroxyeicosatetraenoic acids as their methyl esters trimethylsilyl, allyldimethylsilyl and tert.-butyldimethylsilyl ethers.

The gas chromatographic and mass spectrometric properties of the monohydroxy acids 5-hydroxyeicosatetraenoic acid (5-HETE), 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) as their methyl ester trimethylsilyl, methyl ester allyldimethylsilyl and methyl ester tert.-butyldimethylsilyl ethers were investigated. The gas chromatographic properties of the trimethylsilyl and tert.-butyldimethylsilyl derivatives were found to be excellent while the allyldimethylsilyl derivative required a well deactivated column. The mass spectra of these silyl derivatives with the exception for 12-HETE did not exhibit particularly intense ions in the upper mass region. A quantitative analysis by selected-ion monitoring of the most intense ion in the upper mass region of respective mass spectrum demonstrated that a detection limit in the low picogram range could only be obtained for 12-HETE. Since the mass spectra indicated that the double bonds exerted a strong influence on the fragmentation pattern, the trimethylsilyl, allyldimethylsilyl and tert.-butyldimethylsilyl ethers of the methyl esters of the reduced analogues of the monohydroxy acids were prepared. The saturation of the double bonds completely altered the fragmentation patterns and very intense ions carrying a high percentage of the total ion abundance were found in all of the mass spectra. The developed technique was utilized for measurements of 5-HETE in lung tissue samples from patients with lung cancer.

Synthesis of [18F]2-deoxy-2-fluoro-D-glucose from highly reactive [18F]tetraethylammonium fluoride prepared by hydrolysis of [18F]fluorotrimethylsilane.

18F-Labeled fluorotrimethylsilane was prepared by nucleophilic substitution of chlorotrimethylsilane with reactor produced [18F]fluoride. Hydrolysis of fluorotrimethylsilane by aqueous tetraethylammonium hydroxide followed by removal of water with a mechanical pump gave a powerful source of no carrier added nucleophilic 18F. Reaction of this purified 18F preparation with 4,6-benzylidene-1-beta-O-methyl D-mannopyranoside-2.3-cyclic sulfate was complete in 2 min at 80 degrees C and gave two labeled products with similar retention times on reverse phase HPLC. Allowing for decay and handling losses during deprotection, the maximum yield of [18F]2-deoxy-2-fluoro-D-glucose from no-carrier added tetraethylammonium fluoride was 50%. Incorporation of 18F into organic products was 30% complete in 10 min at room temperature. An identical time-course was observed for reaction of 3-O-triflyl-1,2-5,6-diisopropylidene-D-allofuranose, the starting material for 3-deoxy-3-fluoro-D-glucose. Reaction of tetraethylammonium fluoride with chlorotrimethylsilane was more rapid and much more tolerant of water than the fluorosugar reactions. Chlorotrimethylsilane can be used to recover unreacted 18F from reaction mixtures.

Occurrence of airborne silicon carbide fibers during industrial production of silicon carbide.

Airborne dust from the production of silicon carbide has been analyzed for particle morphology and composition. Fibers of alpha silicon carbide were identified by scanning electron microscopy (SEM) combined with energy dispersive X-ray spectrometry (EDS) and transmission electron microscopy (TEM) with selected area electron diffraction techniques (SAED). Micrographs taken at high magnification revealed several stacking periods along the fiber axis, and one or more of the polytypes 2H, 4H, or 6H could be distinguished. Preliminary investigations applying SEM showed that 80% of the fibers had diameters of less than 0.5 micron and a length greater than 5 micron. Fiber concentrations were examined by the counting of stationary and personal samples in an optical phase contrast microscope. The fiber levels in the three plants investigated were low and less than 1 fiber/cc of air (10(6) fibers/m3). Dust samples from the handling of raw material, including recycled material, contained up to 5 fibers/cc (5 X 10(6) fibers/m3).

Novel silylated steroids as aromatase inhibitors.

Androst-4-en-3-one analogs incorporating a trimethylsilyl or a trimethylsilylmethyl group at C-1, C-2 or C-19 were prepared and evaluated as inhibitors of aromatase. Only 10-[1-hydroxy-2-(trimethylsilyl)ethyl]estr-4-ene-3,17-dione inhibited human placental aromatase. Enzyme kinetic analysis revealed competitive inhibition [apparent dissociation constant (Ki) of 562 +/- 12 nM] associated with marginal time-dependent inhibition.

[Synthesis and study of 5-(trialkylsilyl)pyrimidine nucleosides. A new alpha-2'-deoxynucleoside with antiherpes activity]. / Sintez i izuchenie 5-(trialkilsilil)pirimidinovykh nukleozidov. Novyi alpha-2'-dezoksinukleozid s antigerpeticheskoi aktivnost'iu.

Glycosylation of 5-trimethylsilyl- and 5-triethylsilyluracil as well as 5-trimethylsilylcytosine with 2-deoxy-3,5-di-O-p-toluyl-alpha-D-ribofuranosylchloride and subsequent deacylation led to alpha- and beta-anomers of 5-Me3SidUrd, 5-Et3SidUrd and 5-Me3SidCyd. 1-(alpha-D-Arabinofuranosyl)-5-trimethylsilyluracil was synthesized starting from the derivatives of 2,3,5-tri-O-benzoyl-D-arabinofuranose and then converted to alpha-5-Me3SidUrd via 1-(2,2'-anhydro-alpha-D-ribofuranosyl)-5-trimethylsilyluracil and 1-(2-chloro-2-deoxy-alpha-D-arabinofuranosyl)-5-trimethylsilyluracil+ ++. Out of all synthesized compounds, only alpha-5-Me3SidUrd inhibits the replication of HSV-1 both in vitro and in vivo; it also exerts a pronounced therapeutic effect in guinea pigs with herpes genitalis induced by HSV-2. The resistance of alpha-5-Me3SidUrd to pyrimidine phosphorylases facilitates its antiviral activity in vivo.

Preparation of enol-tert.-butyldimethylsilyl and mixed tert.-butyldimethylsilyl-trimethylsilyl ethers for gas chromatography--mass spectrometry of steroids and bile acids.

Conditions are described for conversion of testosterone into the 3-enol, 17-bis-tert.-butyldimethylsilyl ether derivative without formation of side products. The steroid is treated with tert.- butyldimethylsilylimidazole in heptane at 100 degrees C using sodium formate as catalyst. Derivatives are also formed at different rates of 3-keto-5 alpha, 3 alpha/beta-hydroxy-, 6 alpha/beta-hydroxy-, 7 beta-hydroxy-, 16 alpha-hydroxy-, 17 beta-hydroxy(sec.)- and 20 alpha/beta-hydroxysteroids, whereas hydroxyl groups in 1 beta, 7 alpha, 12 alpha/beta, 15 beta and 17 alpha(tert.) positions do not react to a significant extent. These positions are derivatized by subsequent addition of trimethylsilylimidazole , yielding mixed derivatives which are suitable for gas chromatography--mass spectrometry with selected ion monitoring. Conditions are given for conversion of some biologically important androgens, progestins and bile acids into a single form of derivative. The use of the method is illustrated by an analysis of steroids in a rat testis.

Pulmonary effects of exposures in silicon carbide manufacturing.

Chest x rays, smoking histories, and pulmonary function tests were obtained for 171 men employed in the manufacturing of silicon carbide. A lifetime exposure to respirable particulates (organic and inorganic fractions) and sulphur dioxide was estimated for each worker. Chest x ray abnormalities were related to respirable particulates (round opacities) and to age and smoking (linear opacities). Pulmonary function was affected by respirable particulates (FVC) and by sulphur dioxide and smoking (FEV1). Pleural thickening was related to age. No exposures exceeded the relevant standards; we therefore conclude that the current standards do not provide protection against injurious pulmonary effects, at least in this industry.

Deoxyribonucleoside-3',5'-cyclic silanediyl derivatives: formation and properties.

Formation of 3',5'-O-(dialkylsilanediyl)deoxyribonucleosides was studied. Treatment of deoxythymidine in DMF with bifunctional silylating reagent such as di-t-butyldichlorosilane and diisopropyldichlorosilane in the presence of imidazole gave the expected silanediyl derivatives. The structure was confirmed mainly by NMR spectroscopy. The stability of these cyclic silyl derivatives toward hydrolysis is also described.

Synthesis of 2-(trimethylsilyl)ethyloxycarbonylamino acids and their use in peptide chemistry.

2-(Trimethylsilyl)ethyl-4-nitrophenyl carbonate has been prepared as a new reagent for the introduction of the 2-(trimethylsilyl)ethyloxycarbonyl group into amino acids or amino acid derivatives. The resulting N alpha-protected amino acids were found to represent suitable intermediates for the synthesis of peptides. The amino-protecting group proved to be stable under the usual conditions of peptide synthesis and readily cleaved in selective conditions via fluoride ion-mediated fragmentation.

The preparation of trimethylsilyl derivatives of sodium salts of organic acids.

Evidence is presented to confirm that N,O-bis(trimethylsilyl)acetamide does not form trimethylsilyl derivatives of sodium salts of many organic acids. Further evidence suggests that such derivatives are formed when either hydroxylamine hydrochloride or trimethylchlorosilane are also present. This presents a useful technique of reducing losses of organic acids due to evaporation during lyophilisation by converting them to sodium salts and preparing volatile derivatives for gas chromatography directly from the salt residue.