Shoetsu Konno

Report on the preparation of deuterium-labelled aconitine and mesaconitine and their application to the analysis of these alkaloids from body fluids as internal standard

Improved analysis of aconitine and mesaconitine, highly toxic compounds from Aconitum species, in body fluids by gas chromatography-selected ion monitoring with their deuterium-labelled analogues as internal standards (I.S.s) is described. Deuterium-labelled analogues of aconitine and mesaconitine were synthesized by the substitution of the N-alkyl group for a deuterium-labelled one. The mass spectra of the derivatives of the deuterium labels closely resembled that of the nonlabelled compounds except for an obvious mass shift produced by substitution of the deuterium atoms at N-alkyl groups. Using these deuterium-labelled compounds as I.S.s, the standard curves for aconitine and mesaconitine were linear (r2=0.999 each) in the concentration range of 50 pg to 50 ng, respectively. The detection limit of the alkaloids was 10 pg each per injection. The recovery, accuracy and precision of the analysis were evaluated with three different concentration of spiked human blood and urine (n=5 each). The recovery rates ranged from 97.6% to 101.3% and the standard deviations of the interseries ranged from 2.1% to 3.9%. These I.S.s give us a more precise analysis and may be useful in examining the behavior of these alkaloids in the human body.

Studies on as-triazine derivatives. VIII: Synthesis of 5-substituted 1,2,4-triazines

Synthese de chloro-5 phenyl-3 R-6 triazines-1,2,4 (A) (R=methyl ou phenyl) par deshydroxylation/chloration de R-6 phenyl-3 2H-triazines-1,2,4ones-5; reactions des composes A avec des alcoolates, des amines, des composes a methylene actif et des cetones sur le substituant chloro-5

Studies of as-Triazine Derivatives. XV. Intramolecular Reverse-Election Demand Diels-Alder Reaction of 1,2,4-Triazine Derivatives

This type ring-transformation(intramolecular reverse electron-demand Diels-Alder reaction) was applicable to the corresponding 3,5-diphenyl-1,2,4-triazine-6-carboxylic acid esters. According to the similar manner, benzofuro[2,3-b]pyridines, benzofuro[2,3-c]pyridines, and benzofuro[2,3-d]pyridines were synthesized in satisfactory yields. The Diels-Alder reaction of 3-(2-phenylethynylphenoxy)-1,2,4-benzotriazine afforded 11-phenylbenzofuro[2,3-b]quinoline.

Studies on as-Triazine Derivatives XIII. A Facile Synthesis of Fusaric Acid from Thienyl-as-triazine Derivatives

Reverse electron-demand Diels-Alder reaction of ethyl 6-(2-thienyl)-1,2,4-triazine-3-carboxylate with norbornadiene in boiling p-xylene followed by the elimination of cyclopentadiene (retro Diels-Alder reaction) gave 5-(2-thienyl)pyridine-2-carboxylate. Desulfurization of the thienyl-pyridine with Raney nickel and subsequent saponification afforded fusaric acid (5-butylpyridine-2-carboxylic acid)

Studies of as-Triazine Derivatives. X. Addition Reaction of Phenylmagnesium Bromide with 1,2,4-Triazines

Obtention des derives phenyl-5 puis diphenyl-5,6 puis triaryl-3,5,6 (la derniere addition se faisant avec le bromure de p-methoxyphenylmagnesium)

as-トリアジン誘導体の研究(第19報)血小板凝集抑制活性を持つ2,3-ジアリールピラジン及び2,3-ジアリールピリジン誘導体の合成

4,5-Diphenyl-2-ethoxypyrimidine (1), 3,4-diphenyl-6-ethoxypyridazine (2) and 2,3-diphenyl-5-ethoxypyrazine (3) were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. 2,3-Diphenyl-5-ethoxypyrazine (3) exhibited significant inhibitory activity. Thus, various 5-substituted 2,3-bis(4-methoxyphenyl)pyrazines were synthesized by the nucleophilic substitution reaction of 5-chloro-2,3-bis(4-methoxyphenyl)pyrazine (9). In a similar manner, substituted 2,3-bis(4-methoxyphenyl)pyridines were prepared from 2,3-bis(4-methoxyphenyl)-6-methylsulfonylpyridine (17), which was synthesized by the cycloaddition retro Diels-Alder reaction of 5,6-bis(4-methoxyphenyl)-3-methylsulfonyl-1,2,4-triazine (16) with norbornadiene. Among the compounds prepared, 6-isopropoxy-2,3-bis(4-methoxyphenyl)-pyrazine (10f) showed the most potent inhibitory activity, which was more than the activity of anitrazafen[5,6-bis(4-methoxyphenyl)-3-methyl-1,2,4-triazine.

Synthesis of 6-alkylamino-3-pyridazinecarboxylic acid derivatives from methyl 6-chloro-3-pyridazinecarboxylate

The synthesis of methyl 6-alkylamino-3-pyridazinecarboxylates (4a-c) was accomplished by the following reaction sequence. On treatment of methyl 6-chloro-3-pyridazinecarboxylate (1) with methanolic ammonia, 6-chloro-3-pyridazinecarboxamide (5) was precipitated almost quantitatively, which reacted with primary alkylamines to give the corresponding 6-alkylamino-3-pyridazinecarboxamide (6a-c). These products were smoothly converted into the methyl esters (4a-c) by treatment with methanol in the presence of boron trifluoride etherate. The reaction of 1 with butylamine in THF gave a complicated mixture in which N-butyl-6-chloro-3-pyridazinecarboxamide(2), N-butyl-6-butylamino-3-pyridazinecarboxamide(3), 4b, and 1 were involved

Studies on as-triazine derivatives. XVII, Chlorination of 5,6-dimethyl-3-phenyl-as-triazine

Homolytic chlorination of 5,6-dimethyl-as-triazine with Cl 2 gave 6-dichloromethyl-5-trichloromethyl-as-triazine (I) selectively. Structural determination of I by chemical method and synthesis of 5-amino-6-formyl-as-triazine derivatives are described.