Research

Creating molecules means connecting atoms together while precisely controlling their bonding patterns and three-dimensional stereochemistry to produce new structures that do not exist in nature. Even subtle differences in substituents can determine reactivity, and variations in molecular geometry can dramatically alter physical properties and biological activity. The development of chemical reactions for constructing molecules—and the optimization of conditions to synthesize target compounds efficiently—lies at the heart of organic synthetic chemistry.

Many of the medicines we rely on today originate from natural products found in nature, which are then refined through the power of chemistry. For example, salicin from willow bark and its derivative salicylic acid possess analgesic properties, but cause side effects such as bitterness and gastrointestinal irritation. By contrast, acetylsalicylic acid (aspirin), produced by chemical modification, overcame these problems and has become one of the most widely used medicines in the world.

In this way, organic synthetic chemistry serves as a vital foundation for drug discovery, guiding biologically active substances toward forms that are more effective, safer, and more practical. In our laboratory, we begin from the principle of "making molecules" and pursue research aimed at creating novel biologically active substances and developing synthetic technologies that generate new functions and molecular order.

A central pillar of our research is "asymmetric synthesis." Certain molecules exist in two forms related to each other as mirror images—these are called enantiomers. Although they look alike, the body recognizes them as distinct, and in drug molecules one enantiomer may have the desired therapeutic effect while the other offers little benefit or even causes side effects.

This can be understood by analogy: just as a right-hand glove fits only the right hand, even though the two hands look similar, our bodies distinguish between enantiomers with great precision. To develop medicines with fewer side effects and superior efficacy, it is therefore essential to selectively synthesize only the desired form. "Catalytic asymmetric synthesis" is one of the technologies that achieves this—a highly sophisticated approach that uses a tiny amount of catalyst to produce large quantities of the target molecule with high efficiency and selectivity.

In high school chemistry, students learn about the properties of various molecules and compounds. At the pharmaceutical school level, this knowledge is extended to understanding the roles of molecules in biological phenomena and to designing and creating such molecules from scratch. In drug discovery, it is important not only to achieve excellent functionality, but also to minimize the environmental impact of synthetic processes.

Transition-metal-based inorganic compounds—such as those containing nickel or palladium—have long played a major role as catalysts in conventional organic synthesis. Our laboratory is actively developing molecular transformation reactions that exploit the properties of these inorganic systems. At the same time, the use of heavy metals and rare metals raises concerns about recovery and disposal. This has led us to focus on the inherent potential of organic molecules themselves and to develop "organocatalytic reactions," in which organic molecules serve as the catalysts. Organocatalysis has emerged as an important trend in modern chemistry, enabling sophisticated molecular transformations while reducing environmental burden.

In our laboratory, we pursue the creation of new molecular transformation reactions from both inorganic and organic chemistry perspectives.

Our laboratory aims to realize, using organic molecules, the transformations previously achieved only by metal catalysts, and to unlock molecular transformation reactions once considered impractical. Phosphine oxides—a focus of our research—were once regarded merely as by-products of reactions, sometimes even seen as troublesome molecules. By taking a fresh look at their molecular properties, however, we have opened a new avenue for their use as organic molecular catalysts.

Building on this, we have reported pioneering results in reactions such as the aldol reaction and alkynylation of carboxylic acids. None of these transformations is easy to achieve. Yet by carefully examining the unique character of each molecule and maintaining the drive to turn "impossible" into "possible," we have succeeded in realizing reactions once thought too difficult. The reactions we have developed have been adopted not only within our own laboratory but by other research groups around the world, where they have been applied to the efficient synthesis of pharmaceuticals.

Our goal is not merely to develop innovative chemical reactions. In the living body, countless molecules are in constant motion, continuously changing shape to bring order to biological activity. By imagining the behavior of each individual molecule and seeking to understand how they move, we aim to create new functions from the molecules we synthesize.

The molecules we create become the starting point for medicines that unlock "new functions." The electronic and steric characteristics inherent to each molecule are specifically recognized within the body, providing the basis for a diverse range of pharmacological effects. Precisely designed molecules have the potential to express their intended functions and become medicines.

Moreover, newly obtained molecules do not merely serve as drug candidates—they can also drive innovation in materials science and life science. The creation of new molecular functions leads to new biological activities, making it an essential means of contributing to society through "creating function."