Development of planar chiral paracyclophane-based double hydrogen-bond-donating catalysts applicable to the synthesis of medicines or pharmaceutical candidate compounds

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06979
• 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: Meijo University
• Principal Investigator: Kitagaki Shinji 名城大学, 薬学部, 教授 (20281818)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 二重水素結合供与触媒 / 不斉合成 / [2.2]パラシクロファン / チオウレア / ドミノ型反応 / Michael反応 / 面不斉

Outline of Final Research Achievements

Planar chiral [2.2]paracyclophane (pCp)-based bisthiourea catalyst 1 has been known to give dinitro compounds with high enantioselectivity in Henry reaction, which is an important reaction for synthesis of biologically active compounds. In this study, we modified the structure of catalyst 1 to further improve its reactivity and selectivity. As a result, although we could not obtain results superior to 1, we were able to identify a core structure that is important for reactivity and selectivity. In addition, we designed and synthesized a pCp-phosphine-thiourea catalyst as an acid-base hybridized catalyst, and confirmed that it showed higher reactivity than known catalysts. Furthermore, using catalyst 1, we succeeded in developing the Michael reaction of nitroalkanes to nitrostyrenes and applying the reaction into a domino-type reaction.

Free Research Field

有機化学、合成化学

Academic Significance and Societal Importance of the Research Achievements

チオウレアのように同時に二つのNHが基質の活性化や位置固定に寄与する官能基がキラル骨格に結合した不斉二重水素結合供与触媒は、既に数多く開発されており、環境への負荷が少なく穏やかな条件で反応が進行することから、医薬品合成等での利用が期待され注目されている。しかし、既存触媒のキラル骨格は限定的であり、我々は不斉分子触媒への利用頻度の低いパラシクロファンを用いることにより、独自の反応性・選択性が発現することを期待し、研究を進めている。今回、新規高性能触媒の創成には至らなかったが、不斉二重水素結合供与触媒を用いて複雑な構造を有するキラル化合物の一挙構築に成功し、創薬への貢献に対する可能性を示した。