Establishment of a Convergent Synthesis of Omura Natural Products Evermectins with Novel Structures and Biological Activities

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15962
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Kitasato University
• Principal Investigator: Kimishima Aoi 北里大学, 感染制御科学府, 助教 (10832404)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 全合成 / ケミカルライブラリー / マクロライド

Outline of Final Research Achievements

Thus far, we have achieved the synthesis of vinyl iodide, sulfone, and bisepoxide, fragments of the aglycone of IVM. In addition, the reaction conditions for connecting these three components in two steps were established to synthesize the aglycone upper unit of IVM. The lower unit of aglycone was obtained by decomposition experiments to natural products, and synthesis of aglycone was examined by closed metathesis with the upper unit. However, since the target product could not be obtained, a diester product was prepared by connecting the upper unit and the lower unit using succinic anhydride as a tether in order to improve the flexibility of the substrate by increasing the number of rings, and RCM proceeded as expected to give a conjugated diene product, and the synthesis of aglycone was achieved.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

エバーメクチン(AVM)は、大村智記念研究所において単離された抗寄生虫・殺虫活性を示すマクロライド系天然物である。AVM類の化学修飾により導かれるイベルメクチン(IVM)は、抗感染症薬や抗寄生虫薬として全世界で利用されている。これまでの、AVMの誘導体は半合成的合成されていることから、本研究成果はによって全合成的に多様な化合物ライブラリーが合成できれば、学術的にも社会的にも非常に意義があると考える。