Organic Chemistry Portal
Reactions >> Total Syntheses

Totally Synthetic by Paul H. Docherty, 11 July 2006

Total Synthesis of Pseudo-Brevenal


H. Fuwa, M. Ebine, M. Sasaki, J. Am. Chem. Soc. 2006, 128, 9648-9650.

DOI: 10.1021/ja062524q

Another poly-ether, though with some interesting biological activity; this one seems to have positive effects, increasing tracheal mucus velocity, and thus potentially of use in respiritory disorders. Also, it appears to be a brevetoxin antagonist in vivo. As discussed in the comments surrounding the previous post (ciguatoxin), much of the work relating to ladder-type poly-ethers has been published before, so I’ll stick to the main disconnections.

Firstly, a Suzuki-Miyaura coupling of the main A,B and D,E fragments, building part of the C ring. This was completed using Sasaki’s own methodology involving enol phosphates:

Completing this coupling in over 84% (quoted over two steps), including a stereoselective hydroboration, they set themselves up nicely to complete the C-ring. Once delivered, they then had to couple the left-hand sidechain, containing a difficult tetra substituded olefin. Impressively, they were able to constuct this using a Stille coupling, in its Cu-TC form.

With relatively simple modifications required to complete the right-hand sidechain, they soon delivered the proposed structure for the natural product, but were confronted by ill-matching spectra when compared to the isolated substance. They propose that they have simply made the C-26 epimer of the natural product (the right-most hydroxyl-bearing carbon), so I’m sure we’ll see the complete specimen shortly.