Total synthesis of indole alkaloids containing an indoline spiroaminal framework and evaluation of their anti-infectious activity

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860010
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: Kitasato University
• Principal Investigator: YAMADA Takeshi 北里大学, 大学院感染制御科学府, 助教 (00608367)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 全合成 / インドール / ニトロン / 抗トリパノソーマ / イソシアニド / α-ヒドロキシアミド / ピリドン

Outline of Final Research Achievements

Total synthesis of the indole alkaloids, neoxaline, oxaline and meleagrin A, all containing a unique indoline spiroaminal framework was accomplished through the stereoselective introduction of a reverse-prenyl group to the congesting benzylic carbon of furoindoline, 2-pot transformation of indoline, containing three nitrogen atoms at appropriate positions, to the featured indoline spiroaminal framework and elimination of carbonate assisted by the adjacent imidazole moiety to construct the (E)-dehydrohistidine. The absolute stereochemistry of the neoxaline was elucidated via our total synthesis. Bioactivity screening indicated that some synthetic intermediates exhibited efficacy against Sleeping Sickness parasites (Trypanosoma brucei brucei ) .

Free Research Field

天然物合成