[No. 124] Yoshiyuki Kobayashi

It's a strange thing that after 27 years since graduation and passing the age of 50, the people you meet and the path you've taken start to feel like destiny. Lately, I've come to feel strongly that my present self has been guided by fate.

In high school, I had aspired to enter the School of Medicine. However, in the 1982 entrance exams during my third year of high school, I passed the exams for the Faculty of Science and Technology at Keio and Waseda but failed to get into the national university's and Keio's School of Medicine. Strangely enough, though, I had no desire to spend a year studying to try for the School of Medicine again, and in April of that same year, I enrolled in the Faculty of Science and Technology at Keio University. Looking back, perhaps this was the beginning of my destiny. When I first entered university, perhaps because my high school dream of becoming a doctor had been so strong, I didn't know what I wanted to do. But I received a huge shock in an organic chemistry class during the second semester of my first year, taught by then-Assistant Professor Kuniaki Tatsuta (now Professor Emeritus and Honorary Fellow at Waseda University).

In the first class, the professor spoke about his recent research achievements, which involved the total synthesis of a macrolide antibiotic from D-glucose. This was completely different from the organic chemistry I had learned in high school. The sheer scale of making an antibiotic from sugar was so shocking, and I was simply moved, thinking, "This is what university research is." It was then that I decided to major in organic synthetic chemistry in the future. For my fourth-year graduation research, I was assigned to the Kinoshita-Tatsuta Laboratory, and for the next three years, through my master's program, I was mentored by Professor Tatsuta. His guidance was extremely rigorous. Experiments ran from early morning to late at night, and our three daily discussions were very demanding. I immersed myself in research in an environment filled with a positive sense of tension. My research topic for my master's thesis was the "biomimetic total synthesis of the 14-membered macrolide antibiotic oleandomycin." Thanks to Professor Tatsuta's guidance, I succeeded in the world's first synthesis of polyketide lactone, a biosynthetic precursor, and oleandolide, the aglycone part, which were key compounds in this research, as well as its glycosylation. I was able to summarize this work in four papers. It goes without saying that the research experience and the research philosophy I learned from him form the foundation of my current work.

In 1988, I joined Sankyo Co., Ltd. (now Daiichi Sankyo Co., Ltd.), and for the next 13 years, I was engaged in exploratory research at its chemistry research laboratories. In September of my third year at the company, I was transferred to a group conducting "exploratory research for new drugs based on sugar," where I was tasked with the total synthesis of trehazolin, a glycosidase inhibitor isolated by our company. The keywords from my research at Keio were "sugar, natural products, total synthesis," and I never imagined I would be working with these same keywords at a pharmaceutical company, so I was surprised by this turn of events. In 1994, I earned my degree for this total synthesis work, and even after that, my work continued to revolve around the aforementioned keywords. From 1995 to 1998, I conducted exploratory research on an influenza therapeutic drug (a neuraminidase inhibitor), using sialic acid, a type of sugar, as a motif. During this period, for a year and a half starting in July 1996, I participated in a joint research project in San Francisco, California, with a venture company called Glycomed, Inc., on the search for adhesion inhibitors based on the cell adhesion substance Sialyl-Lewis X. After returning to Japan, I worked on the synthesis of antibiotics. In the end, the focus of my research at the company unexpectedly became the same as it was in my university days, and I felt a strange sense of connection.

From 2003 to 2007, I had my second overseas assignment in the United States (San Diego). This time, my work was more business-oriented, involving research planning and alliances. Then, in October 2007, I returned to Tokyo and was tasked with managing the clinical development of the neuraminidase inhibitor that we had discovered during my time in the research laboratories. It is a rare experience in a pharmaceutical company to be able to personally advance the development of a compound you discovered yourself. Perhaps this was also fate; it felt as if we were drawn to each other, leading me to take charge of this project. The development was extremely difficult, but we obtained approval for treatment in 2010 and for prevention in 2013. It is now used in clinical practice as "Inavir® (product name)," an influenza treatment that completes therapy in a single administration. In 2012, I returned to my old chemistry research laboratories, and in April 2015, I was appointed Director of the Medicinal Chemistry Research Laboratories. There had been no precedent in our company for someone to return to the research laboratories after being away from the research front for about 10 years. Meanwhile, 27 years after joining the company, I realized I had experienced almost every job related to R&D in a pharmaceutical company. I intend to continue to make full use of my experience to discover new drugs.

Although I majored in organic synthetic chemistry at university and have been through many twists and turns, I find myself still continuing my research today. The question "Is this destiny?" still lingers in my mind.