How organic chemistry can contribute to society

Determining the structures of natural products and achieving total synthesis

Professor Seiji Iwasa became interested in the world of organic compounds as a result of his fascination with the miraculous properties of medicinal herbs and other natural products. After that point, guided by his curiosity, he worked toward becoming a researcher in natural products chemistry.

Professor Iwasa says, “Just as Ninjas once used aconite poison as a weapon by wiping it on the tips of their Shuriken, there are many surprising natural products in this world that can take a person’s life even when used in tiny quantities. However, aconite also has beneficial cardiotonic and analgesic effects, and thus has long been used as a medicine as well. That shows that even poison can be a medicine if used properly. Nevertheless, in order to use such products effectively, we need to understand their structures and functions. It is the mission of organic chemists to make these products useful by reproducing them synthetically, a process which is called ‘total synthesis’.”

At that time, Professor Iwasa was working on the total synthesis of strychnine, an extremely toxic alkaloid. The molecular structure of strychnine was uncovered in the mid-20th century after a century of effort. After that discovery, R.B. Woodward et al. succeeded in completing the synthesis of strychnine in 29 steps. Professor Iwasa and his team successfully shortened the process by more than half, to just 12 steps. This was in 1994.

“The method we used is called retrosynthetic analysis, and it involves exploring how to synthesize a substance by breaking down the synthetic process step-by-step while analyzing the molecular structure. This method allowed us to more easily synthesize strychnine. This field deals with molecules, which have a three-dimensional form. Because of this, it requires big leaps in topological thinking and mathematical sense. That is why this research is so thrilling to me,” says Professor Iwasa.

Catalytic asymmetric reactions: A promising tool for drug discovery

In order to seriously investigate the methodology for further shortening and simplifying the process of total synthesis, Professor Iwasa is currently focusing his efforts on the development of catalytic asymmetric synthesis. Asymmetric synthesis is a method of synthesizing optical isomers, which has come to be used in the development of most drugs in recent years.

Professor Iwasa explains the concept. “An optical isomer is a compound that cannot be superimposed on its opposite compound, like a human’s right and left hands. In essence, it is a mirror image of a substance. In the case of most optical isomers, the right-handed one has a therapeutic effect, whereas the left-handed one is toxic. Even though the substances look the same, they have completely opposite physiological properties.”

One well known example of this is thalidomide. Thalidomide, a drug developed as a hypnotic and sedative, caused a global tragedy in 1957 due to the toxicity of one of its isomers, which caused the children of mothers who took the drug while pregnant to be born with limb malformations. When normal methods of synthesis are used, both the right-handed and left-handed optical isomer are produced at the same time. Essentially, this tragedy occurred because both isomers were present in the drug. Therefore, in order to safely use an optical isomer as a drug, it is necessary to skillfully produce just the isomer with the useful properties. This can be done by asymmetric synthesis.

A wide scope of work ranging from molecular sensors to development of drug substances

One of Professor Iwasa’s achievements, that exemplifies the wide-ranging scope of his research, is his project to develop a kit for testing for residual pesticides using immunochromatography. He worked on this project as part of the Food Safety Technology Project, one of the core research projects of Knowledge Hub Aichi, which is run by the Aichi prefectural government. It involves the simple detection of residual pesticides by employing antibody reactions, which are part of organisms’ immune systems, a field of study quite different from total synthesis.

Reporter's Note

After finishing his degree at Chiba University, young Professor Iwasa wrote letters to research institutions all over the world telling them of his desire to pursue the study of organic chemistry. He got his first response from the University of Ohio, despite having no connections there. He then went to the United States, where he achieved several research accomplishments, including the synthesis of strychnine, and later got an offer from the University of Chicago. This moment made him feel how open-minded Americans are and how strong their researcher network is.

In order to return the favor, Professor Iwasa is making an active effort to recruit international students. Students from eight different countries, including China, Mongolia, Laos, and Malaysia, are currently working with him in his laboratory.

“Learning about the world like that has reminded me of what is good about Japan. I want to bring good aspects of Japan such as its advanced technological capabilities, strong morality, and respect for the environment to the rest of the world. To that end, I am currently engaged in Japanese language education in Asia as well,” says Professor Iwasa.

His curiosity is extending beyond his research to education and the environment as well.