A crude product possessing local anaesthetic properties was extracted from the seeds of Xanthoxylum piperitum DC., which was named crude sanshool. Hydrosanshool obtained by its reduction was proved to be N-isobutyl-lauric amide from its decomposition and by mixed fusion with a synthetic product. It is certain that sanshool is an N-isobutylamide of unsaturated fatty acid with C12 and that the anaesthetic properties of Semen Xanthoxylii is derived from this compound. The latter fact can be endorsed by the examples found in spilanthol and fagaramide. During the purification of sanshool, a substance, C15H23O2N, m.p. 111°, with 4 double bonds, was obtained which gave lauric acid and ammonia by decomposition. This compound was named sanshoamide.
In order to examine the reactivity of guanidine residue in acetylsulfaguanidine and sulfaguanidine, formylcyclohexanone was applied on the latter two compounds. Acetyl compound easily reacted with formylcyclohexanone in pyridine solution and the objective compound was obtained. In the case of sulfaguanidine, irrespective of the presence of free amino radical in para-position, only the guanidine group reacted giving a dehydrated (1mol. H O) compound in alcoholic solution and dehydrated (2mol. H2O) and cyclized compound under the presence of NaOC2H5 in an alcoholic solution. The acetal obtained by the treatment of Na-formylacetone with alcoholic HCl easily gives sulfamerazine by either heating to 140-150°, under pressure, in alcoholic solution with acetylsulfaguanidine under the presence of NaOC2H5, or by refluxing over a water bath with sulfaguanidine.
A few improvements were made in the synthetic process of the compound mentioned in the subtitle as an intermediary in the synthesis of rac-emetine-Pyman. By these means, the yield was increased, making it possible to employ the compound as a raw material for the said synthesis.
The intermediate product, 4′, 5′-dimethoxy-6-carboxy-8-methyl-3, 4, 5, 6, 7, 8-hexahydro-(1′, 2′: 1, 2-benzoquinolizine), obtained by the improved synthetic procedure was subjected twice to Arndt-Eistert reaction and a corresponding β-homoveratrylamide was obtained. This compound was then cyclized and reduced to give two racemic compounds of rac-emetine-Pyman. Compared to natural emetine, these compounds are more stable to light and heat.
Utilizing the intermediate compound obtained during synthesis of rac.-emetine-Pyman for the synthesis of isoquinoline nucleus, β-methoxy-β-homoveratrylamine was used and rac-emetiamine-Pyman was obtained.
1) Application of chloro-acetone or chloro-acetophenone on the Na-salt of p-nitrothiophenol results in p-nitrophenylmercapto-acetone and -acetophenone, respectively. Oxidation of the latter 2 compounds give corresponding sulfone-acetone and -acetophenone. Subsequent bromination of p-nitrophenylmercapto-and sulfone-acetones and -acetophenones and their condensation with thiourea give 2-amino-5-p-nitrophenyl-m rcaptothiazole and -sulfonethiazole. 2) Bromination of p-nitrobenzenesulfone-acetone is discussed.
1) 3, 5-Dinitrobenzoate and 8-hydroxyquinoline-5-sulfonate of antimalarials of 8-amino-quinoline series were prepared. These salts were found to be suitable for the isolation of the bas s, purification, identification and storage, as well as for clinical use although the compounds were sparingly soluble in water. 2) 2-Hydroxycinchonate and sulfate were prepared as soluble salts fulfilling all the conditions set above.
1) 6-Methoxy-8 (β-diethylaminoethyl)-aminoquinoline was obtained with comparatively good yield by the condensation of 6-methoxy-8-aminoquinoline and β-diethylaminoethyl benzoate hydrochloride. 2) Chemical changes were observed of the heating of β-diethylaminoethyl benzoate hydrochloride and a course of transition was assumed regarding products obtained thereby.
2-Benzyl-4-ethoxymethylene-5 (4)-oxazolone, etc. were synthesized as the raw materials for the synthesis of penicillin G. In the course of experiments, it was made clear that 4-benzyl-mercaptomethylene compounds transited to 4-mercaptomethylene compound via 4-anilinomethylene compound.
Growth of mold was inhibited in a 50-day test by 2, 4-dihydroxy-benzophenone at a cencentration of ca. 0.005-0.007% and by 2, 4-dihydroxy-3, 6-dimethylbenzophenone at a concentration of 0.010 to 0.015%, Four other compounds tested showed virtually no antiseptic actions.