Development of Novel Catalytic Organic Reactions Using Gaseous Molecule Surrogates for Drug Discovery

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: University of Shizuoka
• Principal Investigator: Konishi Hideyuki 静岡県立大学, 薬学部, 准教授 (20565618)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 気体 / 分子 / 等価体 / 一酸化炭素 / 二酸化硫黄 / カルボニル化 / スルフィド

Outline of Final Research Achievements

We have developed novel catalytic organic reactions applicable to rapid derivatization in drug discovery research using gaseous molecule surrogates that can generate carbon monoxide (CO) and sulfur dioxide (SO2) upon chemical reaction or physical stimulation. In the development of open-air carbonylation reactions using phenyl formate as a CO surrogate, we found that the reversible adduct formation of a base and phenyl formate occurs quickly at the onset of the reaction, contributing to the slowdown of the CO formation process and making the process the rate-determining step in the overall reaction. On the other hand, we have developed a metal-catalyzed formation of symmetrical and unsymmetrical sulfides using iodoarenes and SO2 surrogates. This reaction is the first general synthetic method of sulfides using SO2 surrogates to introduce divalent sulfur atoms.

Free Research Field

有機合成化学、医薬化学

Academic Significance and Societal Importance of the Research Achievements

取扱困難であるがゆえに使用が躊躇されることの多い気体状の化学物質に代わり、これらを化学反応や物理刺激により生成できる取扱容易な固体の「気体分子等価体」と呼ばれる化学物質を用いて、安全性と実用性に優れた新しい化学変換反応の開発を行った。安価で容易に入手可能な気体分子等価体を用いて得られた研究成果は、気体状化合物の新たな反応性の開拓および合成的用途の拡大を実現するものであり、開発した化学反応は有機合成化学において今後さらなる利用が期待される。