Scientific contribution by Prof. Tsuda.

Research accomplishment of Professor Kyosuke Tsuda was summarized and published as “A list of publications by Professor Kyosuke Tsuda and his collaborators” at his retirement from University of Tokyo at the age of 60. His memoir and treatise by his collaborators were published. In addition, the journal Heterocycles published as a commemorative issue for his 75 birthday, in which appeared at the head of the issue “Profile and Scientific Contribution of Professor K. Tsuda” written by Okuda and Ikekawa. Further, as a commemorative event to celebrate his 85 birthday, a gorgeous volume with 500 pages entitled “Sixty fire years with Pharmaceutical Science”, was published seven years ago by a goodwill of Hirokawa Publishing Company, containing memorable photographs, his autobiography, his research and its development, his activities in education and in scientific societies as well as reminiscence by 80 individuals. Thus I feel somewhat hesitant to repeat his academic contributions and his personality in this memorial issue as they already seemed to have been described sufficiently. Prof. Tsuda, however, was one of the founders, and also the editor-in-chief of this journal, and his research accomplishments should be considered to represent the development of pharmaceutical sciences in the twentieth century. When one considers these facts, one realizes the significance of retracing his footprints in this journal, hence I have decided to uptake the task of writing this article even though many repetitions are unavoidable. As complete lists of his research articles have appeared in the above three publications, only main articles are described here. Also, courtesy titles of collaborators are omitted here. Professor Tsuda was borne in 1907, in the city of Kiirun, Taiwan, as the fourth and youngest child to Mr. Sosuke Tsuda, who had been born to a warrior class family, and was an official of the Government-General of Taiwan and engaged, at that time, in the harbor construction of Kiirun. After finishing a primary school in Kiirun, Prof. Tsuda finished a five-year middle school in Taipei in four years, then passed the entrance examination and admitted to Urawa High School at his home area, in the Department of Science, in 1923. He lost his mother when he was in the second year at the high school. He belonged to the swimming team in the high school, and the coach of the club was a young chemist graduated from University of Tokyo. Upon his urging, Prof. Tsuda decided to study at the Department of Pharmaceutical Science, University of Tokyo. The Department at that time had only four laboratories, and upon graduation, he became, at the direction of Prof. Heizaburo Kondo, an assistant to the assistant professor, Dr. Eiji Ochiai in 1929. In the following year, Dr. Ochiai was promoted to an associate professor, and Dr. Tsuda to an assistant professor. A study was initiated in 1885 by Prof. Nagayoshi Nagai on a Chinese herbal medicine, Kujin (SOPHORAE RADIX) which was prepared from dried roots of a leguminous plant, Kurara, and the bitter tasting component was isolated and named matrine (1) by Prof. Nagai. The first report on the study on its structure was published in the ninth volume of Yakugaku Zassi in 1889 by Nagai and Tahara. The struggle of Prof. Tsuda with matrine continued to 1935. During this struggle, Dr. Ochiai went to Germany to study for two years, and Prof. Tsuda was left to do the work by himself. He even worked on the day of his own wedding at his bench in the laboratory. Such dedication would not even be imaginable to the youth of the present time, I suppose. All these were done before the invention of chromatography, and it must have been of utmost difficulty to determine the structure of the oily substance that were produced by chemical reactions. Several hundred grams of potassium salt of matrinic acid (2) was crystallized from the reaction product with potassium hydroxide, and purification of the fraction upon the dry distillation with soda lime yielded at least five products. It took three years for him to identify these products. The work was painstakingly repeated to purify these products by distillation under reduced pressure, formation of their crystalline salts, isolation of the base, and again distillation under reduced pressure. Significant compounds among them were nordehydro-a-matrinidine (3) and dehydro-a-matrinidine (4) which were later synthesized. He also succeeded in obtaining octadehydro derivative (5) of matrine by heating it with a palladium catalyst. Combining these reactions, he finally succeeded in elucidation two-dimensional structure of matrine. This study constituted his doctoral dissertation, which took 6 years in the making. Prof. Kondo was very pleased with his work, and the six years of work formed the basic philosophy for Prof. Tsuda’s research work, i.e., the conviction that a man could find the way to accomplish his goal if he devoted himself thoroughly to his work.