Development and Application of Convergent Strategies for Unified Total Syntheses of Architecturally Complex Natural Products

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253003
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: Inoue Masayuki 東京大学, 大学院薬学系研究科(薬学部), 教授 (70322998)
• Co-Investigator(Renkei-kenkyūsha): URABE Daisuke 東京大学, 大学院薬学系研究科, 講師 (80503515) ; NAGATOMO Masanori 東京大学, 大学院薬学系研究科, 助教 (70634161) ; TAKEFUMI Kuranaga 東京大学, 大学院薬学系研究科, 助教 (70625201)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 合成化学 / 全合成 / 生物活性分子の設計 / 生理活性 / 収束的合成 / ラジカル反応

Outline of Final Research Achievements

Architecturally complex and densely oxygenated natural products often have potent and selective biological activities. In this study, we focused on efficient, practical and flexible syntheses of these natural products based on radical chemistry. We developed an a-alkoxy radical methodology for assembly of two- and three components, and efficient radical-radical homo- and heterocoupling reactions of a-alkoxy radicals. By taking advantage of these strategies, we realized the total syntheses of various complex natural products, including ryanodine, crotophorbolone, 4-hydroxyzinowol, oubagenin, and zaragozic acid C. Moreover, these synthetic routes were applied to unified preparation of the structurally related compounds for the future structure-activity relationship studies. Because of the broadness of the reaction scope and the mildness of the conditions, these powerful strategies introduce novel technologies for expedited total synthesis of densely oxygenated natural products.

Free Research Field

天然物合成化学・生物有機化学