Structure Analysis and Structure-Activity Relationship Study of an Antifungal Natural Product Amphidinol 3

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K17857
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Synthetic chemistry
• Research Institution: Kyushu University
• Principal Investigator: Ebine Makoto 九州大学, 理学研究院, 助教 (70545574)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 有機合成化学 / 天然物化学 / 構造改訂 / 全合成 / 抗真菌活性 / 構造活性相関

Outline of Final Research Achievements

Amphidinol 3 (AM3) is an antifungal marine natural product isolated from the dinoflagellate Amphidinium klebsii. Because of its complex structure and huge molecular size, the determined structure needs to be confirmed. Actually, we previously revised the C2 and C51 configuration by chemical synthesis of partial structure and its chemical correlation, mainly using NMR analysis.
In this research, we carried out 1) the synthesis of C31-C67 part of AM3 and its C32-C38 diastereomer, 2) the degradation of synthetic intermediates to give C33-C50 fragments of proposed AM3 and its and C32-C38 diastereomer, 3) the comparison of their NMR data to those of natural product. These experiments clarified the C32-C36 and C38 configurations of AM3 to be revised, which was further confirmed by first total synthesis. Moreover, structure-activity relationship study using artificial truncated analog suggested that both two THP rings are essential to induce the desired antifungal activity.

Free Research Field

天然物合成化学