Synthesis and reactions of a monosubstituted dithiirane 1-oxide, 3-(9-triptycyl)dithiirane 1-oxide

A 3-monosubstituted dithiirane 1-oxide, 3-(9-triptycyl)dithiirane 1-oxide, was prepared for the first time, by the reaction of (9-triptycyl)diazomethane and S₈O. The dithiirane 1-oxide was obtained as cis- and trans-isomers, and the structure of the trans-isomer was verified by X-ray crystallography. The cis-isomer isomerized gradually to the trans-isomer in solution. The divalent sulfur atom of the cis- and trans-dithiirane 1-oxides were removed on treatment with triphenylphosphine to give the corresponding Z- and E-sulfines, respectively. The reaction of the trans-dithiirane 1-oxide with (Ph₃P)₂Pt(C₂H₄) provided the (sulfenato-thiolato)Pt^II complex, and that with Lawesson's reagent yielded the 1,3,4,2-trithiaphospholane and 1,2,4,5,3-tetrathiaphosphorinane derivatives.     

High-performance liquid chromatographic assay for simultaneous determination of tramadol and its active metabolite in human plasma. Application to pharmacokinetic studies

Summary A sensitive liquid chromatographic assay for the quantitative determination of the opioid analgesic tramadol and its active metabolite is described. Fluconazole was used as internal standard. The assay involved a singletert-butyl methyl ether extraction and LC analysis with fluorescence detection. Chromatography was at 30°C pumping an isocratic mobile phase of acetonitrile-water (19∶81, v/v) containing 0.06M NaH₂PO₄ and 0.05M triethylamine, adjusted to pH 7.90, at 1 mL min⁻¹ through a reversed-phase, 250×4 mm base-stable column. The limit of quantitation of tramadol and its active metabolite was 1 ng mL⁻¹, only 0.5 mL plasma sample was required for the determination. The calibration curve was linear from 1–1000 ng mL⁻¹. Intra and inter-day precision (C.V.) did not exceed 10%. Mean recoveries of 96.38% for tramadol and 96.62% forO-demethyltramadol with CVs of 0.43% and 1.46% were obtained. Applicability of the method was demonstrated by a pharmacokinetic study on normal volunteers who received 100 mg tramadol intravenously.     

A new route to the improved synthesis of 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils

A new route to C-6-selenenyl analogs of compound 1a from 5-alkyl-6-chlorouracils 6a-b has been described. A mild and highly efficient synthesis of 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils 8a-e has been accomplished from 6a-b in good yields using a two step procedure. Silylation of 5-alkyl-6-chlorouracils 6a-b using N,O-bis(trimethylsilyl)acetamide followed by regioselective alkylation of the silylated intermediate with ethyl or benzyl chloromethyl ether in dichloromethane afforded the desired 1-(alkoxymethyl)-5-alkyl-6-chlorouracils 7a-d in 88–94% yields. Compounds 7a-d readily underwent addition-elimination reaction with an appropriate arylselenol in the presence of ethanolic sodium hyroxide to produce the corresponding 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils 8a-e in excellent yields (94–99%).     

2,3-dimethoxyperhydro-1,4,2,3-dioxadiazine: Synthesis,conformation, and conversion to 1-(2-hydroxyethoxy)-2-methoxydiazene-1-oxide. Crystal structure of 1-[2-(para-nitrobenzoyloxy)-ethoxy]-2-methoxydiazene-1-oxide

The oxidation of 1,2-bis(methoxyaminooxy)ethane (3) with PbO₂ afforded 2,3-dimethoxyperhydro-1,4,2,3-dioxadiazine (4) in the form of the 55:45 mixture of thetrans-4ee- andcis-4 isomers. The barrier of the ring conversion (G₂₃₈ =11.3 kcal/mole) of thecis-4 isomer was determined by the method of¹³C NMR. The regio- and stereospecific stereoelectronically controlled reaction of (4) withpara-nitrobenzoic acid gives the equimolar mixture of methylpara-nitrobenzoate and the 1,2-dialkoxydiazene oxide (5), the structure of which, and the (E)-configuration, were shown by the x-ray structural data of its acylation product — the diazene oxide (6).N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2624–2632, November, 1992.     

Novel coordinating motifs for lanthanide(III) ions based on 5-(2-pyridyl)tetrazole and 5-(2-pyridyl-1-oxide)tetrazole. Potential new contrast agents

Water-soluble and neutral Ln(III) and Zn (II) complexes of pyridine- and (pyridine-1-oxide)tetrazole have been synthesized and the Gd derivatives have great potential as high-relaxivity low-osmolarity MRI contrast agents.     

Preparation of 3(5)-phenyl-1-hydroxypyrazole 2-oxide and 4-methyl-3(5)-phenyl-1-hydroxypyrazole 2-oxide

Nitrosation of acrylophenone oxime or of methacrylophenone oxime with n-butyl nitrite in the presence of pyridine and copper(II) sulfate gives the copper complexes of the title compounds. The free 1-hydroxypyrazole 2 -oxides are isolated by treating the copper complexes with dilute sodium hydroxide, filtration, and acidification of the basic filtrates. The title compounds are the first examples of 1-hydroxypyrazole 2 -oxides in which the C3(5) ring position is unsubstituted.     

Analogs of pyrimidine nucleosides. 19. Synthesis,antineoplastic activity,and kinetics of the hydrolysis of 1-(3-phthalidyl)-5-fluorouracils

1-(3-Phthalidyl)-5-fluorouracils were synthesized by alkylation of 2,4-bis(trimethylsilyl)-5-fluorouracil with substituted 3-bromophthalides, and the rate constants for hydrolysis at pH 8.0–11.5 were determined. The antineoplastic activity of a number of the compounds was established, and it was assumed that there is a relationship between the biological activity and the rate of hydrolysis.See [1] for communication 18.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1406–1411, October, 1985.