Biogenetically inspired synthesis of skeletally diverse macrocyclic scaffolds and evaluation of their function

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H02847
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: The University of Tokyo (2020-2021); Tokyo University of Agriculture and Technology (2019)
• Principal Investigator: Oguri Hiroki 東京大学, 大学院理学系研究科(理学部), 教授 (80311546)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 骨格多様化合成 / 生合成摸倣 / マクロ環状分子群 / 中分子 / インドールアルカロイド / ハリシクラミン / 多能性中間体 / 含窒素骨格

Outline of Final Research Achievements

As a synthetic approach to generate variants of natural products, we developed divergent processes to produce systematic collections of skeletally diverse macrocyclic molecules possessing middle-sized molecular weights. To explore biogenetically inspired synthetic approach, we designed and synthesized multi-potent intermediate with installation of appropriate functional groups. We aim to formulate logic and strategies of the divergent synthesis toward generation of skeletally diverse molecules with the control of regio-, stereo- and enantio-selectivities. By synergistically exploiting the versatile reactivities underlying in the multipotent intermediates, we have synthesized densely-functionalized macrocyclic skeletons with wide variation of three-dimensional structures. We have developed a fundamental technology that allows concise and systematic synthesis of small and medium-sized functional molecules relevant to the biologically intriguing natural products.

Free Research Field

天然物化学・有機合成化学・ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

生合成を模倣しつつ有機合成を駆使して柔軟に拡張するアプローチで，天然物を合理的に改変し，生体機能分子の探索資源を現実的なコストで創製する。分子を形作る骨格や立体化学，活性発現に重要な官能基を自在に改変し，生体機能性と構造多様性を兼ね備えた中分子群を系統的に合成する。中分子に特有の分子認識能力を顕在化させるケミカルバイオロジーを展開し，医薬品リード化合物を創出するプラットフォームを開発する。