Search

In the previous papers(1)(2)(3) it was reported that several ω-(3, 4-dihydroxyphenyl) alkanoic esters and ω, ω'-bis-(3, 4-dihydroxyphenyl) alkanes were prepared and were found to have marked antioxydant activities. In the present paper, therefore, synthesis of ω-(2, 5-dihydroxyphenyl) alkanoic esters and ω, ω'-bis-(2, 5-dihydroxyphenyl) alkanes, the isomers of above compounds, were undertaken to search more effective antioxydants. 1) The synthesis of methyl γ-(2, 5-dihydroxyphenyl) butyrate (V): β-(2, 5-Dimethoxyphenyl) propionic acid (I) prepared by the treatment of hydroquinone dimethyl ether with succinic anhydride in the presence of AlCl3, was demethylated with HI to give β-(2, 5-dihydroxybenzoyl) propionic acid (IV). This was then reduced to γ-(2, 5-dihydroxyphenyl) butyric acid (III) by the CLEMENSEN reduction and was then esterified. 2) The synthesis of methyl e-(2, 5-dihydroxyphenyl) caproate (XIII): Hydroquinone dimethyl ether was condensed with polymeric adipic anhydride in the presence of AlCl3 to give δ-(2, 5-dimethoxybenzoyl) valeric acid (VIII). This acid was reduced by the CLEMENSEN reduction to give e-(2, 5-dimethoxyphenyl) caproic acid (X). The demethylation of (X) with HI gave e-(2, 5-dihydroxyphenyl) caproic acid (XI), which was esterified in the usual way. 3) The synthesis of 1, 6-bis-(2, 5-dihydroxyphenyl) hexane (XIV): Two moles of hydroquinone dimethyl ether were condensed with one mole of adipyl chloride in the presence of AlCl3 to give 1, 4-bis-(2, 5-dimethoxybenzoyl) butane (IX), which was reduced by WOLF-KISNER method to 1, 6-bis-(2, 5-dimethoxyphenyl) hexane (XIII) and was then demethylated. 4) The synthesis of 1, 10-bis-(2, 5-dihydroxyphenyl) decane (XVII): This compound was prepared in 'the same way as in (XIV), using sebacoyl chloride and hydroquinone dimethylether as starting materials. The antioxydant activities of these compounds will be discussed in the following paper. The authors wish to express their appreciation to Professor Dr. Y. SUMIKI for his guidance and advice.

In the previous paper(1)(2) it was reported that some of the ω, ω'-bis-(3, 4-dihydroxyphenyl) alkanes showed remarkable antioxidant activites equal or superior to that of NDGA. Therefore, in the present paper syntheses of ω, ω'-bis-(3, 4-dihydroxyphenyl) butane and hexane were exa-mined from the practical standpoint. (1) the preparation of 1, 4-bis-(3, 4-dihydroxyphenyl) butane. The. synthetic method of ω, ω'-bis-(3, 4-dihydroxyphenyl) butane described in the previous paper(3) was so complicated that the examination of alternative processes seemed to be necessary. Firstly, ω-bromoacetoveratrone was treated with aqueous KOH in ethanol to yield 1, 2-diverat-roylethylene according to the BOGOSLOVSKII's method(4), but this attempt was unsuccessful. Then, the method of LUTL(7) to give 1, 2-dibenzoylethylene by the condensation/of benzene and fumaryl chloride was applied for veratrol but the corresponding dibenzoylethylene was not obtained. Next, in order to prepare 1, 4-diveratrylbutane via 1, 2-diveratroylethane, ω-bromoace-toveratrone was converted into car-cyanoacetoveratrone, m.p. 137_??_138° and the both compounds were condensed to give 1-cyano-1, 2-diveratroylethane, m.p. 148_??_149°, but the yield of the first step was so low such as 36% that this method should also be given up. Finaly, the processes from vsratrol and succinic anhydride to yield 1, 4-diveratrylbutane reported in the previous paper(3) were re-examined and the following results were obtained. The yield of 1-veratroyl-3-(3.4-dimethoxy-6-bromophenyl) propane from γ-(3, 4-dimethoxy-6-bromophenyl) butyric acid was found to increase from 13% to 60% when the chloroform solution of the latter compound was treated with SOCl2 in the presence of a trace of-dry pyridine. Then, 1, 4-diveratrylbutane was obtained in 90% yield by hydrogenating 1-veratryl-4-(3, 4-dimethoxy-6-bromophenyl) butane with Raney Ni and KOH in ethanol at 12 atm. and 63°. (2) The preparation of 1, 6-bis-(3, 4-dihydroxyphenyl) hexane. In this series, the ruduction of 1, 4-diveratroylbutane was found to be the most difficult step as was described in the previous paper(3) but it was solved by the following method. 1, 4-Di-veratroylbutane was hydrogenated to give 1, 6-diveratrylhexane with Pd-charcoal in ethanol-acetic acid at atmospheric pressure and room temperature., in the theoretical yield. Also with Cu-CrO in ethanol at 160° for 4 hrs with an initial pressure 40 atm. in 70% yield. 1, 6-Bis-(3, 4-dihydroxyphenyl) hexane was obtained by refluting 1, 6-diveratrylhexane with powdered AlCl3 in anhydrous chlorobenzene for 4 hrs at 140_??_150°. The authors wish to express their appreciation to Professor Dr. Y. SUMIKI for his guidance and advice

カイコを被検昆虫として,経口投与により薬用植物中の昆虫生理活性物質を検索する過程で,次のことが明らかになった. (1) 漢方薬ニクズク末がカイコ幼虫の成育を阻害し,ある場合には三眠蚕を出現させた. (2) このような成育阻害活性をもたらすものとして,ニクズク末より単離されたghenylpropanoidsならびに,それらの関連物質のカイコの成育に対する影響をしらべたところ,メチレンジオキシ基や,多数のメトキシル基を持つ化合物が,顕著な阻害活性を示した. (3) これらのphenylpropanoidsのうち,化合物IIIは50ppmで4令カイコ幼虫に対して摂食阻害的作用を示し,化合物Vは100ppmで4令カイコ幼虫に対して毒物的作用をあらわし, 90%致死させた.

薬用植物に含まれる昆虫生理活性物質を検討する過程で,漢方薬オウギ末がカイコの変態を阻止することを知り,活性の本体を追求したところ,活性成分としてL-canavanineが単離された.オウギ末中のL-canavanine含量は約0.22%であり,この化合物を5ppm人工飼料に加えて5令起蚕カイコ幼虫に経口投与すると,その50%が化蛾できずに斃死する.このようなカイコ変態阻止物質が化学的に明らかにされたのは,これが初めてである.

新しい昆虫生理活性物質の単離を目的として,種々の薬用植物を人工飼料に混入したのち,カイコ幼虫に経口投与して,それらが幼虫の成育にどのような影響を与えるかを観察した.その結果, (1) 黄柏,三黄散,毛黄連,苦木,コンズランゴ,木通に成育阻害活性が認められた.これらのうち,黄柏の活性成分はberberineと同定された. (2) 檳榔子,苦棟皮には殺虫作用が認められた.これらのうち,檳榔子の活性成分はarecolineと同定された. (3) 丁字,肉豆〓には成育阻害物質あるいは,三眠蚕を誘起する物質の存在が予想された. (4) 黄著は,カイコ幼虫を上蔟後に斃死させ,その活性成分はL-canavanineと同定された.