A novel synthesis of substituted quinolines using ring-closing metathesis (RCM): its application to the synthesis of key intermediates for anti-malarial agents

A method for synthesizing substituted quinolines using ruthenium-catalyzed ring-closing metathesis as a key step has been developed. Substituted 1,2-dihydroquinolines, 4-silyloxy-1,2-dihydroquinoline and 4-methoxy-1,2-dihydroquinoline, were successfully synthesized in excellent yields via ene-ene metathesis and silyl or alkyl enol ether-ene metathesis, respectively. The synthetic intermediates of the antimalarial agents quinine, chloroquine, and PPMP-quinine hybrid were efficiently synthesized by this methodology.     

Synthesis of 2-[2-(8-hydroxyquinolyl)azo]-1-naphthol and its use in the spectrophotometric determination of calcium in potable water

The synthesis of a novel reagent, 2-[2-(8-hydroxyquinolyl)azo]-1-naphthol (HQAN), is described. The acidity constants of the reagent and its reactions with various metal ions are reported. The HQAN reagent forms a soluble calcium chelate in 50% (v/v) dioxane/ water at pH > 8.5 (? = 24 000 l mol^?1 cm ^t-1 at 570 nm). It also forms chelates with magnesium, other alkaline earth metals, and ivalent Mn, Fe, Ni, Cu, Zn, Cd and Pb. These interferences (except for Mn) can be avaoided by pH adjustment or by adding masking agents, and a very simple procedure for the determination of calcium in potable waters is obtained.     

KINETICS OF 4-THIOURIDYLATE-SENSITIZED PHOTOINACTIVATION OF RIBONUCLEASE A

Abstract —An action spectrum for the inactivation of ribonuclease A photosensitized with 4-thiouridylic acid follows the shape of the absorption spectrum of an RNase-thiouridylate complex or of the unbound nucleotide. The quantum yield is 3.3 times 10^-3. Statistical analysis of the data suggests that only the bound nucleotide participates in the photoinactivation. An Arrhenius plot for the first-order rate constants of inactivation gives a straight line in the range 0–40C and an apparent activation energy of photoinactivation of 5.7 kcal/mol. The 4-thiouridylate-sensitized photoinactivation of ribonuclease A is regarded as a kind of photodynamic action in which the substrate analogue plays the role of photosensitizer.     

Synthesis of new dihydropyrazines with DNA strand-breakage activity

Treatment of 1,2-cyclohexanedione with 1,2-diamines, e.g. ethylenediamine and cis-(and trans-)1,2-diaminocyclohexane, caused [4+2] cyclocondensation to give the corresponding dihydropyrazine derivatives (compounds 1-6). They exhibited stronger DNA strand-breakage activity than that of dihydropyrazines, which has already been reported in previous papers.     

A High Sensitivity Fluorescent Chemo-sensory System Based on β-Cyclodextrin Dimer Modified with Dansyl Moieties

-Cyclodextrin dimer linked with ethylenediamine at the upper rim of the cyclodextrin has been synthesized and then modified with two dansyl moieties inthe presence of N,N'-dicyclohexylcarbodiimide. The sensing ability and bindingproperty of the title compound were investigated for steroids and terpenoids. Thefluorescence intensity of this dimer was decreased when a host–guest complex was formed. The value I/I⁰, where I⁰ and I are fluorescence intensitiesin the absence and presence of a guest and I is I⁰- I, was used as a parameter of sensitivity. This host exhibited a much higher sensitivity and selective molecular recognition ability for bile acids such as ursodeoxycholic acid andchenodeoxycholic acid and terpenoids such as (-)-borneol than the dansyl-modifiedcyclodextrins reported previously including -cyclodextrin dimer. The behaviors of the appended moieties of the host during the formation of host–guest complexes were studied using induced circular dichroism (ICD) and fluorescence spectra. The ICD intensityof this dimer was decreased on accommodation of a guest and this spectral pattern of the title dimer was opposite to that of bis dansyl-modified -cyclodextrin monomer. Theguest-induced variations in the fluorescence and ICD intensities suggest that this dimer formed a 1 : 1 host–guest complex and the appended moieties act as a hydrophobic cap.     

New synthesis of 5-amino-5-deazaflavin derivatives by direct coupling of 5-deazaflavins and amines

5-Amino-5-deazaflavin derivatives are newly synthesized by direct coupling of 5-deazaflavins and amines. Some of them revealed potential activity toward tumor cells such as L1210 or KB cells.     

Preparation and separation of all possible rotamers of a stereochemical analog of meso-tartaric acid: optically inactive and optically active isomers of (R,S)-2,2′-bis(methoxycarbonyl)-6,6′-dimethyl-9,9′-bitriptycyl

All the three possible rotamers of the title compound were separated by chromatography, and unambiguously identified by NMR and X-ray analysis. One of the isomers was optically inactive C_i conformation. The other optical active forms were resolved to give a pair of enantiomers, which were characterized by optical rotation and CD spectra. Thus the optical inactivity of a compound such as meso-tartaric acid that can take C_i conformation in solution, is now ascribed to that the molecule has an optically inactive C_i conformer and equal amounts of optically active conformers, that are enantiomers, in solution.     

Physicochemical properties and stability in the acidic solution of a new macrolide antibiotic, clarithromycin, in comparison with erythromycin.

Clarithromycin (6-O-methylerythromycin), a new 14-membered macrolide antibiotic, has been studied to clarify its physicochemical properties and stability in acidic solution, as compared with erythromycin (EM). The solubility of clarithromycin (CAM) in distilled water was lower than that of EM and decreased with increasing temperature. The solubilities of CAM and EM in the phosphate buffer solution at 37 degrees C decreased with an increasing pH and kept constant above pH 9. From pH-solubility profiles, the dissociation constants of CAM and EM were determined to be 8.76 and 8.36, respectively. The partition coefficient of CAM took a higher value than that of EM and increased with an increasing pH. In the acidic solution, the decomposition of CAM and EM obeyed the pseudo-first order kinetics. From the decomposition rate constants, the half life (T1/2) of CAM and EM were determined. In pH 1.39, CAM degraded with a T1/2 of 17 min while EM kinetics corresponded to a T1/2 of 3 s. Therefore, CAM was 340-fold more stable in pH 1.39 and markedly more stable in the acidic solution than EM.     

Some pyridylazo compounds as sensitive reagents for the spectrophotometric determination of nickel

Six 2-(2-pyridylazo)-5-alkoxyphenol derivatives were synthesized, and their application to the spectrophotometric determination of nickel was studied; 2-(2-pyridylazo)-5-methoxyphenol and the corresponding ethoxyphenol are very sensitive and selective. The molar absorptivity of the nickel chelate of the former is 11.3 × 10⁴ l mol^-1 cm^-1. A solvent extraction procedure for the selective determination of 1–8 μg of nickel is described.