Abstract
Laetirobin, isolated from a parasitic fungus host-plant relationship, was synthesized in six practical steps with an overall yield of 12% from commercially available 2,4-dihydroxyacetophenone. Because the product is a pseudosymmetric tetramer of benzo[b]-furans, each step of the synthesis was designed to involve tandem operations. Highlights include: 1) the double Sonogashira reaction of a bisACHTUNGTRENUNG(alkyne), 2) the practical copper(I)-mediated formation of a bisACHTUNGTRENUNG(benzo[b]furan), and 3) the biomimetic [4+2] dimerization and unexpected cationic [5+2] annulation of gem-diaryl alkene precursors. Preliminary structure-activity relationship data between the isomeric [4+2] and [5+2] tetramers revealed only the natural product to possess promising anticancer potential. Specifically, laetirobin is capable of blocking tumor cell division (mitosis) and invoking programmed cell death (apoptosis).
Original language | English |
---|---|
Pages (from-to) | 342-351 |
Number of pages | 10 |
Journal | Chemistry - An Asian Journal |
Volume | 5 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2010 Feb 1 |
Keywords
- Antitumor agents
- Biomimetic synthesis
- Cycloaddition
- Dimerization
- Total synthesis
ASJC Scopus subject areas
- Biochemistry
- Organic Chemistry