Based on organic chemistry, we aim to synthesize highly functional organic compounds that are useful for drug discovery and medical treatment. To this end, we are also focusing on the development of new synthetic methods and catalysts for the rapid and convenient synthesis of natural organic compounds with unique chemical structures and remarkable biological activities, as well as their various derivatives. The project is characterized by the exploitation of untapped potential of representative elements, transition metals and enzymes, and the integration of their properties.

Enzymes, which are born from nature through fermentation and return to it through degradation, exhibit extremely high chemoselectivity, stereoselectivity, and catalytic turnover at round room temperature and ordinary pressure. Therefore, they are one of the ideal catalysts for sustainable material production. We are working on the development of methods to construct chiral drug candidates with complex molecular structures by utilizing the excellent enantiodiscriminating ability of lipases, easy-to-handle hydrolases among diverse enzymes. Recent achievements include dynamic kinetic resolution, asymmetric desymmetrization, and synthesis of optically pure molecules by one-pot sequential reactions, developed by combining latest organic synthetic methods with enzymatic reactions.

The introduction of fluorine into bioactive compounds often improves their metabolic stability, membrane permeability, and other desirable properties as pharmaceuticals. Half of the fluorinated drugs currently on the market have fluorine substitutions in the benzene ring, but methods for introducing fluorine at desired positions in the benzene ring are still limited. To further expand the potential of small molecule drug discovery, We have developed a method to replace either one of the two hydroxyl groups in the catechol structure, which is often found as a structural motif in natural products, with fluorine at the desired position. By applying this method to natural products and synthetic compounds containing catechol moieties, the creation of novel drug discovery candidates is underway.

Benzynes, having a triple bond in the benzene ring, exhibit extremely high chemical reactivity and have been used for the one-step synthesis of polysubstituted and/or fused benzenes. However, it has been difficult to control the reaction positions of the benzynes. By introducing a boron, silicon, oxygen, or bulky substituent into the adjacent position of the benzyne’s triple bond, we have achieved the reaction site control as desired. Another advantage of this method is that the commanding substituents can be converted into other substituents in subsequent steps. This achievement paves the way for the fewer-step synthesis of a variety of polysubstituted and/or fused aromatic compounds by direct coupling of benzynes with other components. We are currently promoting research aimed at the practical application of this method.