New Stereoselective Methodology for the Synthesis of Dihydroxerulin and Xerulin, Potent Inhibitors of the Biosynthesis of Cholesterol

A new stereoselective methodology for the synthesis of both dihydroxerulin and xerulin has been devised. The key step required cross-coupling reactions between the bromo trienyne, (1E,3E,5E)-1-bromo-8-trimethylsilyl-1,3,5-octatrien-7-yne and the appropriate conjugated diynes. The palladium-catalyzed tandem cross-coupling/cyclization reaction of the resulting polyenynes with (Z)-3-iodo-2- propenoic acid led directly to dihydroxerulin or xerulin with a high degree of stereoselectivity.