Reverse aromatic cope rearrangement of 2-allyl-3-alkylideneindolines driven by olefination of 2-allylindolin-3-ones: synthesis of alpha-allyl-3-indole acetate derivatives

The reverse aromatic Cope rearrangement of 2-allyl-3-alkylideneindolines obtained by Horner-Wadsworth-Emmons olefination of 2-allylindolin-3-ones was performed. When 2-allylindolin-3-ones were treated with phosphonium ylides in refluxing toluene, domino Wittig reaction and reverse aromatic Cope rearrangement took place to give alpha-allyl-3-indole acetate derivatives in good yields. The aromatization as a new driving force in the Cope rearrangement is preferable to the conjugation with the carbonyl and cyano groups and also to the alkyl substitution pattern, which are well-known driving forces.     

A simple and simultaneous determination of acyclovir and ganciclovir in human plasma by high-performance liquid chromatography

A simple high-performance liquid chromatographic method was developed for the simultaneous determination of the therapeutic levels of acyclovir and ganciclovir in human plasma. After precipitation of plasma proteins with 6% perchloric acid, acyclovir and ganciclovir were simultaneously determined by reversed-phase chromatography with spectophotometric detection at 254 nm. The peak heights for acyclovir and ganciclovir were linearly related to their concentrations ranging from 0.063 to 2.080 micro g/mL. The recovery was 100.48-102.84% for acyclovir and 99.26-103.07% for ganciclovir. The intra- and inter-day relative standard deviation values were in the range 0.186-8.703% for acyclovir and 0.137-6.424% for ganciclovir. The detection limits for both compounds were 0.01 micro g/mL determined as the signal-to-noise ratio of 3. The present method is applicable to therapeutic monitoring during antiviral medication.     

Reaction of enaminones with carbon disulfide: Synthesis of heterocycles using enamino dithiocarboxylates

Reaction of various types of enaminones, which are prepared by the condensation of 1,3-dicarbonyl compounds with aromatic amines, with carbon disulfide in the presence of sodium hydroxide as the base in dimethyl sulfoxide to give the corresponding enamino dithiocarboxylates, 1,3-thiazines and trithiones. Enamino dithiocarboxylates are cyclized under refluxing in diphenyl ether to give the fused quinoline derivatives. The reaction of 6-arylamino-1,3-dimethyluracils with excess carbon disulfide in the presence of sodium hydroxide and subsequent methylation with dimethyl sulfate gave directly the corresponding 1,3-dimethyl-5-methylthiopyrimido[4,5-b]quinoline-2,4(1H,3H)-diones.     

Determination of sodium and chlorine in pure water by neutron activation analysis

Neutron activation analysis was applied to determine sodium and chlorine in high purity water samples. After irradiation of the sample,³⁸Cl was purified from⁸²Br and other nuclides by carbon tetrachloride extraction and silver chloride precipitation, and²⁴Na was separated from other alkali elements and other nuclides by adsorption of²⁴Na on HAP. The activities of both elements were measured by conventional G.M. counter. The contamination of the elements from container walls during neutron irradiation and the interference with³⁸Ar(n, p)³⁸Cl reaction on argon dissolved in water were also examined. Water samples containing 3 ppb of chlorine could not be determined accurately, owing to the above mentioned interfering reaction.     

Elongation and contraction of molecular springs. Synthesis, structures, and properties of bridged [7]thiaheterohelicenes

A series of bridged [7]thiaheterohelicenes 3a-c and 4 with a variety of helical pitches have been prepared from racemic and optical pure 2,13-bis(hydroxymethyl)dithieno[3,2-e:3',2'-e']benzo[1,2-b:4,3-b']bis[1]benzothiophene (1) in order to investigate the helical structures in solution. Recrystallizations of (PM)-3a, (PM)-3b, (PM)-3c, and (P)-4 from hexane-dichloromethane gave crystals suitable for X-ray crystallography, while recrystallization of (PM)-4 with benzene gave an inclusion complex with a stoichiometry of (PM-4)(4).(C(6)H(6)). X-ray analyses of (PM)-3a-c, (PM-4)(4).(C(6)H(6)), and (P)-4 indicate that the dihedral angles between terminal thiophene rings of the helical framework significantly vary from 22 degrees for 4 to 59 degrees for 3c. This represents as increase of 37 degrees or 168%. Although the (13)C NMR and UV absorption spectra of bridged helicenes 3a-c and unbridged helicene 5 are essentially the same, the molar rotation of 5 is very large compared with those of 3a-c and 4. A red shift (15 nm) in the circular dichroism (CD) spectrum is observed for 4, suggesting that this compound is more planar than 3a-c in solution. In the series of [7]thiaheterohelicenes studied, the minimum helical pitch is 2.70 A for 4.     

Formation of Supramolecular Polymers Constructed by Cyclodextrins with Cinnamamide

-Cyclodextrin having cinnamamide at 6- or 3-positions (6-CiNH--CD, 3-CiNH--CD) and -cyclodextrin with cinnamamide on 6-position (6-CiNH--CD) have been prepared. Supramolecular structures were formed in the solid state or aqueous solutions and characterized by measurements of NMR and vapor pressure osmometry (VPO). The results indicate that 6-CiNH--CD formed insoluble supramolecular polymers in the solid state, while 6-CiNH--CD and 3-CiNH--CD formed supramolecular complexes in aqueous solutions. 6-CiNH--CD was found to form a dimer in an aqueous solution. 3-CiNH--CD formed intermolecular complexes to give supramolecular polymers. The differences of the position of guest part on cyclodextrins caused to give a variety of supramolecular structures in aqueous solutions.     

Simultaneous determination of sulfamethoxazole and trimethoprim in human plasma by capillary zone electrophoresis

A capillary electrophoretic method for the simultaneous determination of sulfamethoxazole and trimethoprim in plasma was developed. Sulfamethoxazole and trimethoprim extracted from human plasma with ethyl acetate were analyzed at 20 kV and 25 degrees C using 15 mm phosphate buffer (pH 6.2) as the electrolyte. The detection was by UV at 220 nm. The run time was 8.0 min and the limit of quantification was 10.00 microg/mL for sulfamethoxazole and 2.00 microg/mL for trimethoprim. The recovery was >99% for both compounds. This method enabled the detection of sulfamethoxazole and trimethoprim in plasma of patients after oral ingestion of their combined formulation. The present simple and rapid method is applicable to drug monitoring in immunocompromised patients who are taking the combined formulation of these compounds for the treatment or prophylaxis of Pneumocystis carinii pneumonia.     

Synthesis of pyrimidine derivatives using N-bis(methylthio)methylenecyanamide

N-Bis(methylthio)methylenecyanamide ( 1 ) was allowed to react with active methylene compounds (methyl cyanoacetate, dimethyl malonate, ethyl acetoacetate, ethyl phenylacetate) in the presence of potassium carbonate or potassium hydroxide in dimethyl sulfoxide followed by the treatment using appropriate a base or an acid to give the corresponding 6-methylthiouracil derivatives in 15–80% yields. These uracil derivatives are found to be useful intermediates for the synthesis of 6-aminouracils and fused pyrimidine derivatives.