Selective transformation of amides for late-stage functionalization

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06974
• 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: Kyoto Pharmaceutical University (2020-2021); Kyoto University (2019)
• Principal Investigator: Kobayashi Yusuke 京都薬科大学, 薬学部, 准教授 (90509275)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アミド / 糖鎖修飾 / ハロゲン結合 / 後期修飾 / 光反応 / ナイトレン / 有機触媒

Outline of Final Research Achievements

Derivatization of biologically active compounds, especially at the late-stage, is one of the most powerful strategy for drug discovery. Although various transformation of relatively reactive amino (-NH2), mercapto (-SH), carboxylic (-COOH), and hydroxyl groups (-OH) have been reported, the neutral amide group (-CONH2) is hard to be derivatized, due to its relatively poor reactivity. In this work, several new methods for the derivatization of amides have been achieved by originally developed catalysts and reagents.

Free Research Field

有機化学

Academic Significance and Societal Importance of the Research Achievements

これまでに報告例のないアミドの直截的な分子変換法を達成することができた。例えば、アミド基しかもたないテモゾロミドのような医薬品のプロドラッグ化が可能となり、医薬品開発を大幅に加速することが期待できる。また、合成の終盤での修飾反応は効率的に多様な誘導体を合成できるため、医薬品の構造活性相関研究に多大に貢献することができる。