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C型肝炎ウイルス（HCV）感染者は、世界に１億人以上いるとされている。先進国では先端的な医薬品の開発で、HCVを病原とする慢性及び急性C型肝炎の治癒率は飛躍的に高まった。一方、世界には経済的に、また医療体制の問題から、それら先端医薬品を手に入れ難い地域も多い。我々は安価で、また手に入れやすいC型肝炎治療薬を開発するために、各地の伝統薬物（生薬）に着目した。特にタンニンを多く含んだ13生薬を選び、メタノールエキスを作成した。HCVの感染に必須であるHCVタンパク質分解酵素を、大腸菌で生成し、この組み換え酵素に対する阻害効果をスクリーニングした。13のエキスのうち６のエキスの100 μg/mlに、90％以上のHCVタンパク質分解酵素阻害効果を認めた。ポリフェノール含量の高いエキス（800-1500 μgGAE/ml）が阻害効果も高い傾向であったが、阿仙薬エキスはポリフェノール含量が高い（1300 μgGAE/ml以上）にも係らず、ほとんど阻害効果がなかった。一方柿蔕エキスは、ポリフェノール含量は比較的低かったが（400 μgGAE/ml以下）、高い阻害活性が認められ、ポリフェノールの種類によっても、阻害活性が異なることが示唆された。今後柿蔕の活性成分について、さらに詳しく研究する。, Aiming at finding novel hepatits C virus (HCV) drugs having easier access and requiring less economical burden, we studied on crude drugs for anti HCV protease activity. Thirteen crude drugs which are known rich in tannins were selected, since we had found peel and seeds of a tropical fruit in Peru, Camu camu, and their tannic ingredients were effectively inhibited the recombinant HCV protease. Methanolic extracts of the crude drugs were tested for inhibitory activity on the enzyme reaction, and 6 of them at a concentration of 100 μg/ml inhibited the reaction more than 90 %. Five of these effective extracts contained as much as 800-1500 μgGAE/ml phenolics, but the extract of kaki calyx (KC) contained less than 400 μgGAE/ml. On the other hand, that of gambir (Ga), which contained more than 1300 μgGAE/ml phenolics, did not effectively inhibit the reaction. We now focus on the effective ingredients contained in the extract of KC.

第43回石油・石油化学討論会 （北九州） セッションID: 1C16, 可溶化・接触分解から成る2段階反応プロセスによるリグニンからのフェノール類の製造を検討した。本研究では、可溶化反応における反応条件の最適化を行うと共に、リグニンの低分子化機構を検討し、フェノール類収率の向上を図った。その結果、反応条件の最適化によるフェノール類収率の向上に成功し、リグニンの低分子化は、構成単位間の全結合のうち約6割を占めるエーテル結合の加水分解により進行することを明らかにした。

第41回石油・石油化学討論会（山口） セッションID: 2E08, 木質バイオマスの主要成分であるリグニンは、アルキルフェノールの重縮合体であり、樹脂原料として需要の高いフェノール等の樹脂原料芳香族への転換が期待される。そこで本研究では、新規リグニン転換法として、リグニンを高温・高圧下で低分子化する段階と、得られたリグニン構成２量体や単量体を酸化鉄触媒により接触分解する段階から成る２段反応プロセスの開発を目的とし、各段階の反応形式と反応条件の最適化を検討した。

Article, 信州医学雑誌 28(4): 367-374(1980)

Article, 信州医学雑誌 31(6): 522-528(1983)

It was shown in the previous papers that the electro-solution voltage of each metal might be closely correlated to the induction or the rate of the reaction between various metals and benzyl chloride. Futher-more inhibiting or promoting action of some reagents for the reaction between aluminum partic1es and benzyl chloride was reported as an attempt to checking the solvent effect of these reagents on the reaction catalyzed by aluminum chloride. Now using similar additives the reaction between iron powder and benzyl chloride is studied from the same stand-point as is stated above. The result obtained is as follows: (1) Mercaptans, amines and amides showed strong inhibiting action, and alcohols showed moderate inhibiting action, whereas most of phenols, nitrobenzene and aluminum triphenolate showed remarkable promoting action. (2) It is shown that the form of curve representing the inhibiting or promoting effect is deservedly changed with the variety of the additives and also inf1uenced with temperature in cosiderable extent. (3) The promoting effect of nitrobenzene reinforced our suggestion for the presence of suitable range of electric conductivity over which the intermediate complex in the system of catalytic reaction with metallic halide is activated by the ionization or polarization of that in desirable degree. (4) One presumption is offered for the explanation of the promoting action of phenols ascribing to the formation of metallic phenolates as the intermediate of the reaction., 著者らはハロゲン化ベンジルと各種の金属との反応についてその進行が金属の電溶圧と密接な関連があることを第1報および第3報において報告したが，後者においてはアルミニウム粒と塩化ベンジルとの反応に対する種々の添加物の影響についてそれらの阻害あるいは促進の様相を塩化アルミニウム触媒反応に対する広い意味の溶媒効果の検討を含めて行なったものである。本報では鉄粉と塩化ベンジルとの反応について略類似の添加物類を使用して同じ立場からの研究を進めたものである。

Our studies of this series which have been reported as "Studies on the Reactivity of Some Halogenohydrocarbons with Various Metals. No. I--VI." were chiefly related to the reaction between benzyl halides or their derivatives and various metals, and also to the promoting or inhibiting action of some organic reagents for these reactions. In one of these reports, the promoting action of small quantities of phenols for the self-condensation reaction of benzyl chloride with gritty aluminum was shown . In this report, for the case of the existing quantity of phenols to benzyl halides being 1:1 or the more in mol ratio the reaction of dehydrohalogeno-condensation with aluminum was checked. Futhermore, it is investigated that the self-condensation of benzyl halides and the benzylization of phenols both occur simultaneously as competitive reaction. The result obtained is as follows: (i) From the determinated values of mean molecular weight for respective reaction products, it was shown that the benzyl halides were mostly di-benzylized and the phenols mainly mono-benzylized. (ii) The proportion of benzyl phenols in these reaction product was increased by the order of phenol, m-cresol>o-cresol>p-cresol for the mol ratio 1:1 and by the increasin g of mol numbers of phenols used . The elevation of reaction temperature increased, not altered and decreased this proportion for mol ratio 1:1, 2:1 and 3:1 respectively., 著者らはハロゲン化ベンジルまたはその誘導体と金属類との反応，ならびにそれらの反応に対する各種の有機試薬類の添加効果などについての一連の研究結果を「ハロゲン化炭化水素と金属類との反応性の研究第1～6報」として報告しているが，そのうちの第3報では金属Alによる塩化ベンジルの自己縮合反応が少量のフェノール類の添加によって促進されることについて述べておいた。本報ではハロゲン化ベンジルとのモル比が1:1またはそれ以上のフェノール類が存在する場合のAlによる脱ハロゲン化水素縮合の反応について検討し，ハロゲン化ベンジルの自己縮合とフェノール類のベンジル化の反応とが同時競争反応として起こることを認めたので，その詳細について報告する。

In the previous paper,it was our investigation that the self-condensation of benzyl halides and the benzylization of phenols both occur simultaneously as competitive reaction when the mixtures of phenols and benzyl haildes,in which the existing quantity of the former to the latter being 1:1 or the more in mole ratio,were treated with gritty aluminum for the condensation by dehydrohalogenat ion. Since these reactions with aluminum needed the addition of some quantity of nitrobenzene,similar reactions with iron is now carried out without this addition. The results obtained are as follows: (i) Using iron powder,benzylization of phenols by benzyl halide smoothly proceeded to the considerable yield,and it is presumed that the iron halide produced as the intermediate product may catalyze the alkylation. (ii) From the determined values of mean molecular weight for the respective reaction products,it was shown that the phenols were mono- and di-benzylized,and the benzyl halides di- and tri- benzylized. (iii) Some information was obtained for the reaction temperature dependance of mean molecular weight of self-condensation products and benzyl phenols having maximum at the specific reaction temperature for respective sort of phenols. (iv) In the benzylization of phenols,p-benzyizlation was easier at lower temperature and o-benzylization at higher temperature., 前報では，フェノール類とハロゲン化ベンジルとの混合物の金属アルミニウムによる脱ハロゲン化水素反応においては，ハロゲン化ベンジルの自己縮合とフェノール類のベンジル化の反応とが同時競争反応として起こることを認め，両反応生成物の性質や生成比率の反応条件による変化などについて述べた。しかし，その場合にはある量のニトロベンゼンの共存を必要としたので，本報ではそれを要しない鉄粉を触媒とする場合について同様な研究を行なったものである。

ln the previous papers it has been believed that the reaction between various metals and benzyl halides or alkyl chlorides is ionic considering the relation between the induction period with each metal and their electro-solution voltage. Now inhibiting or promoting power of some reagent for the reaction between aluminum particles and benzyl chloride is studied and checked also their solvent effects. The result obtained is as follows: (1) 4 sorts of mercaptans retarded this reaction whereas many alcohols and phenols promoted them, and further this promoting action is increased in accordance with lowering the reaction temperature and extremely enhanced by optimum quantity of these reagents at 70℃. (2) For the 5 sorts of amines the order of inhibiting power was benzyl-> β-naphthyl-> α-naphtyl-> aniline> lauryl-. This resembled with the orders of inhibiting power of alcohols and mercaptans for the reaction between aluminum particles and carbontetrachlorde as benzyl-> phenyl-> lauryl-. (3) The addition of ligroin showed the promoting effect over the considerable wide range in which the range of 1.O--10.5g was striking and the addition of nitrobenzene also showed the promting effect over the range of 0.05--0.5g. This solvent effect was remarkable rather than resemble to that of the reaction between aluminum particles and carbontetrachloride, and this results would support our presumption for the presence of suitable range of electrolytic conductivity over which the system of catalytic reaction with metallic halide acts ionically., 第1報はハロゲン化ベンジルと各種の金属との反応について，第2報は3種の塩化アルキルと各種の金属あるいは塩化金属との反応についての報告であって，これらにおいて反応の進行は金属の電溶圧と密接な関連があることを認めて，これらの反応がイオン的であることを指摘しさらに塩化ベンジルと銅，鉄，アルミニウムとの反応については無極性の溶媒であるリグロインの添加によって反応が緩和されあるいは促進されることを認めている。本報ではアルミニウム粒と塩化ベンジルとの反応について添加物の影響を広い意味の溶媒効果の検討を含めて行ったものである。