Synthesis and Biological Activity of the QRS Ring System of Maitotoxin
Access this Article
Maitotoxin (MTX) is a ladder-shaped polyether produced by an epiphytic dinoflagellate. As a part of our structure–activity relationship studies using synthetic partial structures of MTX, the QRS ring comprising a 6/6/7 tricyclic system was synthesized through stereoselective construction of five contiguous stereogenic centers on the Q ring via i) coupling of a Weinreb amide and a furyllithium, followed by ii) Noyori asymmetric transfer hydrogenation, iii) the Achmatowicz reaction, iv) chemoselective methylation of a methyl acetal in the presence of a carbonyl group by treatment with Me<sub>2</sub>Zn/BF<sub>3</sub>·OEt<sub>2</sub>, v) highly diastereoselective dihydroxylation, and vi) ring expansion of a six-membered to a seven-membered ring ketone. The synthetic specimen inhibited MTX-induced Ca<sup>2+</sup> influx with an IC<sub>50</sub> value of 44 µM.
- Chemistry Letters
Chemistry Letters 43(12), 1904-1906, 2014
The Chemical Society of Japan