Synthesis of bioactive compounds

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860065
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Natural medicines
• Research Institution: Nagoya Institute of Technology (2015); Osaka University (2014)
• Principal Investigator: Sumii Yuji 名古屋工業大学, 工学(系)研究科(研究院), 助教 (10612848)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 海洋天然物 / 全合成 / 構造活性相関 / アナログ合成 / 細胞増殖抑制物質 / 抗結核物質 / ケミカルバイオロジー

Outline of Final Research Achievements

We developed enantioselective synthesis of (+)-dictyoceratin-A and -C, hypoxia-selective growth inhibitors, from marine sponge. We tested the in vitro bioactivity of both enantiomers, and found that both enantiomers showed same hypoxia-selective growth inhibitory activity. We evaluated in vivo anti-tumor activity and structure-activity relationships of analogues of dictyoceratin-A and -C. We found that the whole structure of 1 or 2 is important for the hypoxia-selective growth inhibitory activity. We also synthesized bioactive probe molecular based on 1 and 2.
We succeeded the total synthesis of 3-alkylamino demethyl(oxy)aaptamine (3), an anti-dormant mycobacterial substance from marine sponge. We confirm the in vitro anti-dormant mycobacterial activity of 3. We also improved the synthetic methodology of 3 and successfully prepared hundreds milligram of 3. Moreover, we synthesized some analogues of 3 and found important information of structure-activity relationships.

Free Research Field

生物活性天然物の全合成およびアナログ合成