Convergent synthesis of dimeric alkaloids possessing highly complex structures based on the development of catalysts for aerobic oxidation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06936
• 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: Tohoku University
• Principal Investigator: Ueda Hirofumi 東北大学, 薬学研究科, 講師 (50581279)
• Co-Investigator(Kenkyū-buntansha): 小林 長夫 信州大学, 繊維学部, 特任教授 (60124575)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 天然物 / アルカロイド / 二量体化合物 / 酸素酸化 / 鉄触媒 / フタロシアニン / 全合成

Outline of Final Research Achievements

In this research, we conducted synthetic studies on dimeric natural products with highly complex structures, which are expected to be utilized as lead compounds for drug discovery, based on the development of enzyme-mimicking catalyst for aerobic oxidation. We achieved the efficient asymmetric total synthesis of pleiocarpamine and deoxoapodine, which contained in pharmaceutically important dimeric alkaloids. The establishment of the highly concise and scalable synthetic method of monomers is expected to allow efficient synthesis of their dimeric alkaloids in near future. Furthermore, our originally developed dimerization was applied to not only natural product synthesis but also dimerization of peptides. These results would contribute to the development of pharmaceutical sciences by developing novel and useful methodologies for the synthesis of natural products and chemical modification of peptides.

Free Research Field

創薬科学

Academic Significance and Societal Importance of the Research Achievements

天然化合物の中には、天然からの単離量が乏しく、かつ複雑な構造のため化学合成による供給が困難であり、創薬研究において埋没した化合物が数多く存在する。本研究では、薬としての可能性を秘めているにも関わらず、化学合成が困難な二量体構造を持つアルカロイドに焦点を当て、新たな化学合成法の提供を通じて、化合物の医薬品シーズとしての可能性を引き出す。本方法論の確立は、新たな医薬品シーズの発掘に繋がるだけでなく、医薬品を安価かつ大量に供給可能な低分子創薬の発展は、近年社会問題の一つである医療費高騰の抑制につながることが期待される。