Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1392754 | European Journal of Medicinal Chemistry | 2013 | 5 Pages |
•Starting from spiromamakone, a more synthetically accessible template was designed.•A total of 50 compounds were rapidly constructed and their cytotoxicity was evaluated.•(±)-7d-II was discovered to be a 15-fold more cytotoxic agent than spiromamakone.•(±)-7d-II appeared to act in a manner similar to spiromamakone.
The spirocycle is a key structure found in many bioactive compounds. From the cytotoxic and spirocyclic natural product, spiromamakone A (1) and its analogues, a more synthetically accessible spiroacetal template 4 was designed based on structural similarity analysis. A total of 50 compounds were rapidly synthesized in only one or two synthetic steps from the starting compound, and their cytotoxicity was evaluated. As a result, (±)-(2R*,5R*)-2-(4-iodophenyl)-7-chloro-1,4-dioxa-spiro[4.5]deca-6,9-dien-8-one (7d-II) was discovered and found to be fifteen-fold more cytotoxic than 1. The easily accessible spiroacetal 7d-II appeared to act in a manner similar to the highly oxidized natural product, spiromamakone A (1).
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide