Arundic acid, synthesis

Very recently, Cozzi et al. successfully demonstrated the application of this methodology for the a-alkylation of the formyl group to enohzable aldehydes. This was achieved by a reaction of benzodithiolylium tetrafluoroborate (a stabilized carbenium ion) in the presence of several different substituted imidazolidin-4-ones [48]. After reductive removal of the benzodithiol group access to chiral a-branched primary alcohol is given. Using this method optically pure arundic acid is obtained by a three-step synthesis. 

The introduction of a 1,3-benzodithiol group in a stereoselective fashion can be used to generate an anionic or cationic equivalent and could be easy removed by Raney nickel. This procedure was applied to the synthesis arundic acid [34], which is currently undergoing phase 11 development for the treatment of acute ischemic stroke, and to the bisabolane skeleton (P. Canestrari, E. Emer, A. Gualandi, and P.G. Cozzi, unpubUshed results). The procedure was recently extended to the formation of quaternary stereogenic centers, in particular the alkylation of a-branched aldehydes with the benzodithiolyUum ion can be catalyzed by the use of 9-amino-9-deoxy-epi-dnchona alkaloid primary amines [35]. The use of primary... 

Pelotier B, Holmes T, Piva O. Synthesis of anti-Alzheimer (R)-arundic acid. Tetrahedron Asymm. 2005 16 1513-1520. 

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