Studies towards total synthesis of anti-HIV conocurvone and construction of trimeric structure using benzyne intermediates

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06975
• 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: Hiroshima University
• Principal Investigator: Kumamoto Takuya 広島大学, 医系科学研究科(薬), 教授 (50292678)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: ベンザイン / クロメン / Diels-Alder 反応 / 抗 HIV / ３量体 / コノクルボン / 環化付加反応

Outline of Final Research Achievements

The total synthesis of anti-HIV active conocurvones with trimeric chromenoquinone structure was investigated based on the Diels-Alder (DA) reaction of trifuran and optically active chromene-derived benzynes. The intramolecular SNAr of fluorinated cinnamic alcohols allowed the efficient synthesis of the desired optically active chromenes. In the synthesis of linked furanones, two types of furanones with side chains were synthesized. We also investigated the synthesis of a simple trimeric structure that is expected their anti-HIV activity, using mucobromic acid as a starting material, which has two leaving groups and a furanone structure. Synthesis of the trimer structure was achieved by the introduction of azide groups and subsequent DA reaction of the azides and benzyne.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

オーストラリア原産植物が産出するコノクルボンが抗 HIV 活性をもつことに着目し，本化合物とその類縁体の合成を検討した．コノクルボンはクロメノキノン構造が３つ連続した構造をもち，３つの連結したフラン環に３分子のクロメン環を反応させることでその構造を構築することとした．このうち，クロメン環の光学活性体の効率的合成法を確立し，さらに３つの連結したフラン環の原料となる側鎖をもつフラノンの合成を達成した．